2016 |
Clancy RL, Dunkley ML, Sockler J, Mcdonald CF, 'Multi-site placebo-controlled randomised clinical trial to assess protection following oral immunisation with inactivated non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease', Internal Medicine Journal, 46 684-693 (2016) [C1]
Background: Previous studies identified factors that modify response to an oral non-typeable Haemophilus influenzae (NTHi) vaccine in chronic obstructive pulmonary disease (COPD):... [more]
Background: Previous studies identified factors that modify response to an oral non-typeable Haemophilus influenzae (NTHi) vaccine in chronic obstructive pulmonary disease (COPD): severe COPD, moderate-severe exacerbations as end-point and a threshold prevalence of NTHi in the study population. More data are needed to confirm parameters that influence clinical outcomes. Aims: The primary aim was to determine the efficacy of an oral NTHi vaccine (HI-164OV) in reducing the rate of exacerbations requiring systemic corticosteroids or hospitalisation in COPD. Secondary aims included effect on the proportion of patients experiencing such exacerbations, severity of infections and quality of life (St George Respiratory Questionnaire for COPD patients (SGRQ-C)). Methods: This multi-centre, double-blind, placebo-controlled study was conducted at 21 Australian sites for 9 months in 2011. Results: Three-hundred and twenty subjects with COPD, FEV1 <60% predicted and =1 moderate-severe exacerbations in the previous 12 months were recruited. The primary and secondary end-points for the intention-to-treat population aged 40-88 years were not achieved, and only 5% of subjects had an H. influenzae-positive sputum sample. Subsequent exploratory analysis of patients <65years (91 subjects) indicated protection with respect to the primary and most of the secondary end-points, with SGRQ-C symptom scores lower at 3 and 6 months. Conclusion: Patients aged 40-88 years with moderate to severe COPD and low rates of H. influenzae-positive sputum were not protected against exacerbations by HI-1640V. Further studies are needed to confirm protection in subjects aged <65years. Older age and low colonisation rates appear to affect adversely response to this vaccine.
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Nova |
2012 |
Essilfie A-T, Simpson JL, Dunkley ML, Morgan LC, Oliver BG, Gibson PG, et al., 'Combined haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma', Thorax, 67 588-599 (2012) [C1]
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Nova |
2011 |
Essilfie A-T, Simpson JL, Horvat JC, Preston JA, Dunkley ML, Foster PS, et al., 'Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease', PLoS Pathogens, 7 e1002244 (2011) [C1]
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Nova |
2011 |
Clancy RL, Dunkley ML, 'Acute exacerbations in COPD and their control with oral immunization with non-typeable Haemophilus influenzae', Frontiers in Immunology, 2 1-6 (2011) [C1]
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Nova |
2011 |
Clancy RL, Dunkley ML, 'A vaccine to prevent exacerbations in COPD', Medical Journal of Australia, 195 99-100 (2011) [C3]
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2010 |
Clancy RL, Dunkley ML, 'Oral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection', Clinical and Experimental Immunology, 161 127-133 (2010) [C1]
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Nova |
2010 |
Tandon MK, Phillips M, Waterer G, Dunkley ML, Comans P, Clancy RL, 'Oral immunotherapy with inactivated nontypeable haemophilus influenzae reduces severity of acute exacerbations in severe COPD', Chest, 137 805-811 (2010) [C1]
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Nova |
2008 |
Cripps AW, Sutton P, Beagley K, Robertson S, Dunkley ML, 'Mucosal immunology down under: Special Interest Group in Mucosal Immunology workshop, Australasian Society for Immunology, Sydney, Australia, 2 December 2007', Immunology and Cell Biology, 86 557-561 (2008) [C2]
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Nova |
2006 |
Cripps AW, Peek K, Dunkley ML, Vento K, Marjason JK, McIntyre ME, et al., 'Safety and immunogenicity of an oral inactivated whole-cell Pseudomonas aeruginosa vaccine administered to healthy human subjects', Infection and Immunity, 74 968-974 (2006) [C1]
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Nova |
2006 |
Vorobjova T, Ren Z, Dunkley ML, Clancy RL, Maaroos HI, Labotkin R, et al., 'Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence', APMIS, 114 372-380 (2006) [C1]
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Nova |
2005 |
Ren Z, Borody TJ, Pang GT, Dunkley ML, Clancy RL, Xia HHX, et al., 'Evaluation of anti-Helicobacter pylori IgG2 antibody for the diagnosis of Helicobacter pylori infection in western and Chinese populations', Alimentary Pharmacology & Therapeutics, 21 83-89 (2005) [C1]
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2005 |
Ren Z, Borody T, Pang GT, Li L-C, Dunkley ML, Clancy RL, 'Selective reduction of anti-Helicobacter pylori IgG subclass antibody in gastric carcinoma', Journal of Gastroenterology and Hepatology, 20 1338-1343 (2005) [C1]
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2003 |
Dunkley ML, Rajyaguru S, McCue AL, Cripps AW, Kyd J, 'Pseudomonas aeruginosa-specific IgG1 and IgG2 subclasses in enchancement of pulmonary clearance following passive immunisation in the rat', FEMS Immunology and Medical Microbiology, 39 37-44 (2003) [C1]
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2003 |
Thomas LD, Kyd JM, Bastin DA, Dunkley ML, Cripps A, 'Immunisation with non-integral OMPs promotes pulmonary clearance of Pseudomonas aeruginosa', FEMS Immunology and Medical Microbiology, 37 155-160 (2003) [C1]
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Nova |
2001 |
Dunkley ML, Clancy RL, 'Influenza-induced bacterial infection: reduced number of airway macrophages', International Congress Series, 0 581-585 (2001) [C1] |
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2001 |
Ren Z, Pang G, Clancy R, Chen Li L, Soon Lee C, Batey RG, et al., 'Gastric Carcinoma: T-Cell Response and Vascularity. Shift of the gastric T-cell response in gastric carcinoma', Journal of Gastroenterology and Hepatology, 16 142-148 (2001) [C1]
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Nova |
2001 |
Ren ZG, Pang G, Clancy R, Li LC, Lee CS, Batey R, et al., 'Shift of the gastric T-cell response in gastric carcinoma', JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 16 142-148 (2001)
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2000 |
Thomas LD, Dunkley ML, Moore R, Reynolds S, Bastin DA, Kyd JM, Cripps AW, 'Catalase immunization from Pseudomonas aeruginosa enhances bacterial clearance in the rat lung', Vaccine, 19 348-357 (2000) [C1]
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2000 |
Ren Z, Pang GT, Lee R, Batey R, Dunkley ML, Borody T, Clancy RL, 'Circulating T-cell response to Helicobacter pylori infection in chronic gastritis', Helicobacter, 5 (3) 135-141 (2000) [C1]
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2000 |
Ren Z, Pang GT, Batey R, Routley D, Russell A, Musicka M, et al., 'Non-urease producing Helicobacter pylori in chronic gastritis', Australian & New Zealand Journal of Medicine, 30 (5) 578-584 (2000) [C1]
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1999 |
Black C, Eyers F, Dunkley ML, Clancy RL, Beagley KW, 'Major histocompatibility haplotype does not impact the course of experimentally induced murine vaginal candidiasis', Laboratory Animal Science, 49, No.6 668-672 (1999) [C1]
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1999 |
Ren Z, Pang GT, Musicka M, Dunkley ML, Batey R, Beagley KW, Clancy RL, 'Coccoid forms of Helicobacter pylori can be viable', Microbios, 97 153-163 (1999) [C1]
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1999 |
Black C, Eyers F, Russell A, Dunkley ML, Clancy RL, Beagley KW, 'Increased severity of Candida vaginitis in BALB/c nu/nu mice versus the parent strain is not abrogated by adodptive transfer of T cell enriched lymphocytes', Journal of Reproductive Immunology, 45 1-18 (1999) [C1]
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1999 |
Dunkley ML, Harris S, McCoy R, Musicka M, Eyers F, Beagley L, et al., 'Protection against Helicobacter pylori infection by intestinal immunisation with a 50/52-kDa subunit protein', FEMS Immunology and Medical Microbiology, 24 221-225 (1999) [C1]
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1999 |
Clancy RL, Corrigan E, Dunkley ML, Eyers F, Beagley KW, 'Recurrent vulvovaginal candidiasis - allergy or immune deficiency?', Int Arch Allergy Immunol, 118(2-4) 349-350 (1999) [C1]
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1999 |
Clancy RL, Dunkley ML, Pang GT, 'In favor of a tolerant respiratory tract', Mucosal Immunology Update, 7, No.4 15-17 (1999) [C1] |
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1998 |
Corrigan E, Clancy RL, Dunkley ML, Eyres F, Beagley KW, 'Cellular immunity in recurrent vulvovaginal candidasis', Clinical Experimental Immunology, 111 574-578 (1998) [C1]
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1998 |
Black C, Eyers F, Russell A, Dunkley ML, Clancy RL, Beagley KW, 'Acute Neutropenia Decreases Inflammation associated with murine vaginal candodiasis but has no effect on the course of infection', Infection and Immunity, 66, No. 3 1273-1275 (1998) [C1]
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1997 |
Cripps AW, Dunkley ML, Clancy RL, Kyd J, 'Vaccine strategies against Pseudomonas aeruginosa infection in the lung.', Behring Institute Mitteilungen, 262-268 (1997)
Pseudomonas aeruginosa is an environmentally ubiquitous, extracellular opportunistic gram-negative bacteria that causes significant morbidity and mortality to a disproportionately... [more]
Pseudomonas aeruginosa is an environmentally ubiquitous, extracellular opportunistic gram-negative bacteria that causes significant morbidity and mortality to a disproportionately high degree for infections with this bacteria compared with other gram-negative bacteria. Patients at particular risk of infection are those with compromised respiratory function, in intensive-care support and taking immunocompromising pharmaceutical agents. Once acquired, infection is difficult to eradicate with chemotherapy and attempts to vaccinate against infection have been of little success. Over the past five years, we have pursued the concept of mucosal immunisation against respiratory infection with P. aeruginosa. Initial studies in an acute animal model clearly demonstrated that mucosal immunisation with a killed whole bacterial cell preparation could induce protective immune responses in the lung. Subsequent studies have shown that the protective immune mechanisms were dependent on antigen specific CD4+ T cells, the activation of alveolar macrophages, the recruitment and activation of polymorphs, predominantly neutrophils, the controlled secretion of TNF-alpha, IL-1 and IFN gamma and the presence of antibody. We have hypothesised that the protective response is under the control of T cells. A pre-clinical human trial of an oral whole killed cell preparation has been completed with no adverse side effects. A limited open trial in patients with bronchiectasis has also been completed. Preliminary analysis of the results has demonstrated that after oral vaccination, specific lymphocyte responses were observed to P. aeruginosa.
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1995 |
CRIPPS AW, DUNKLEY ML, CLANCY RL, KYD J, 'PULMONARY IMMUNITY TO PSEUDOMONAS-AERUGINOSA', IMMUNOLOGY AND CELL BIOLOGY, 73 418-424 (1995)
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1995 |
WILSON NR, DUNKLEY ML, BURET A, YOUNG B, CRIPPS AW, 'HISTOPATHOLOGY OF THE LUNG FOLLOWING INTRATRACHEAL CHALLENGE WITH LIVE PSEUDOMONAS-AERUGINOSA IN INTESTINALLY IMMUNIZED RATS', IMMUNOLOGY AND CELL BIOLOGY, 73 440-445 (1995)
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1995 |
DUNKLEY M, PABST R, CRIPPS A, 'AN IMPORTANT ROLE FOR INTESTINALLY DERIVED T-CELLS IN RESPIRATORY DEFENSE', IMMUNOLOGY TODAY, 16 231-236 (1995)
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1995 |
CRIPPS AW, DUNKLEY ML, CLANCY RL, KYD J, 'Pulmonary immunity to Pseudomonas aeruginosa', Immunology and Cell Biology, 73 418-424 (1995)
Pseudomonas aeruginosa, an oportunistic bacterial pathogen, is a major course of morbidity and mortality in subjects with compromised respiratory function despite the significant ... [more]
Pseudomonas aeruginosa, an oportunistic bacterial pathogen, is a major course of morbidity and mortality in subjects with compromised respiratory function despite the significant advances in therapeutic practices. The bacteria produces an armoury of products which modify its infective niche to ensure bacterial survival. The role of antibody in protection against pulmonary infection remains poorly defined. Protection appears to be associated with opsonizing antibody whilst some other antibody responses may be deleterious and promote further lung damage. Cell mediated responses are clearly important in protection against infection. This review proposes a vaccine strategy aimed at enhancing specific T cell responses in the lung which, through T cell-derived cytokines, drive the recruitment of neutrophils to the lung and the subsequent activation of these cells results in the clearance of bacteria from the lung. Copyright © 1995, Wiley Blackwell. All rights reserved
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1995 |
WILSON N, DUNKLEY M, BURET A, YOUNG B, CRIPPS A, 'Histopathology of the lung following intratracheal challenge with live Pseudomonas aeruginosa in intestinally immunized rats', Immunology and Cell Biology, 73 440-445 (1995)
This paper examines the histology of rat lungs following intestinal immunization with killed mucoid Pseudomonas aerugtnosa and subsequent pulmonary challenge with live P. aerugino... [more]
This paper examines the histology of rat lungs following intestinal immunization with killed mucoid Pseudomonas aerugtnosa and subsequent pulmonary challenge with live P. aeruginosa. The lungs of non-immune challenged rats developed a confluent haemorrhagic pneumonitis with degeneration and sloughing of the mucosa of the airways; perivascular infiltration with mononuclear cells was apparent 1¿2 h post-challenge; some neutrophils were present by 2 h post-challenge; by 12h post-challenge oedema and intra-alveolar haemorrhage were prominent and Gram-negative organisms were seen in large quantities. In contrast, immunized challenged animals showed a pronounced neutrophilic response 1¿2 h post-challenge; by 12 h post-challenge patchy abscesses were apparent with resolving inflammation and no organisms visible. The findings suggest that intestinal immunization prevents the development of fatal P. aeruginosa infections in the lung by accelerating the recruitment of polymorphonuclear neutrophils Copyright © 1995, Wiley Blackwell. All rights reserved
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1995 |
CLANCY R, PANG G, DUNKLEY M, TAYLOR D, CRIPPS A, 'ACUTE ON CHRONIC-BRONCHITIS - A MODEL OF MUCOSAL IMMUNOLOGY', IMMUNOLOGY AND CELL BIOLOGY, 73 414-417 (1995)
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1995 |
KYD JM, DUNKLEY ML, CRIPPS AW, 'ENHANCED RESPIRATORY CLEARANCE OF NONTYPABLE HAEMOPHILUS-INFLUENZAE FOLLOWING MUCOSAL IMMUNIZATION WITH P6 IN A RAT MODEL', INFECTION AND IMMUNITY, 63 2931-2940 (1995)
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1994 |
CRIPPS AW, DUNKLEY ML, CLANCY RL, 'MUCOSAL AND SYSTEMIC IMMUNIZATIONS WITH KILLED PSEUDOMONAS-AERUGINOSA PROTECT AGAINST ACUTE RESPIRATORY-INFECTION IN RATS', INFECTION AND IMMUNITY, 62 1427-1436 (1994)
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1994 |
DUNKLEY ML, CLANCY RL, CRIPPS AW, 'A ROLE FOR CD4(+) T-CELLS FROM ORALLY IMMUNIZED RATS IN ENHANCED CLEARANCE OF PSEUDOMONAS-AERUGINOSA FROM THE LUNG', IMMUNOLOGY, 83 362-369 (1994)
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1994 |
BURET A, DUNKLEY ML, PANG G, CLANCY RL, CRIPPS AW, 'PULMONARY IMMUNITY TO PSEUDOMONAS-AERUGINOSA IN INTESTINALLY IMMUNIZED RATS - ROLES OF ALVEOLAR MACROPHAGES, TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERLEUKIN-1-ALPHA', INFECTION AND IMMUNITY, 62 5335-5343 (1994)
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1993 |
KYD J, DUNKLEY M, CLANCY R, CRIPPS A, 'VARIATION IN PROTECTION FOLLOWING IMMUNIZATION WITH P6 TO NONTYPABLE HAEMOPHILUS-INFLUENZAE CHALLENGE', JOURNAL OF LEUKOCYTE BIOLOGY, 112-112 (1993) |
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1993 |
BURET A, DUNKLEY ML, CRIPPS AW, 'EFFECTOR MECHANISMS OF PULMONARY IMMUNITY TO PSEUDOMONAS-AERUGINOSA FOLLOWING INTESTINAL IMMUNIZATION', AMERICAN REVIEW OF RESPIRATORY DISEASE, 147 A204-A204 (1993) |
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1993 |
BURET A, DUNKLEY M, CLANCY RL, CRIPPS AW, 'EFFECTOR MECHANISMS OF INTESTINALLY INDUCED IMMUNITY TO PSEUDOMONAS-AERUGINOSA IN THE RAT LUNG - ROLE OF NEUTROPHILS AND LEUKOTRIENE B4', INFECTION AND IMMUNITY, 61 671-679 (1993)
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1993 |
DUNKLEY ML, MADSEN G, HUSBAND AJ, 'HETEROGENEITY OF HELPER T-CELL SUBSETS IN PEYER PATCHES', IMMUNOLOGY LETTERS, 37 181-186 (1993)
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1993 |
DUNKLEY ML, BURET AG, CRIPPS AW, 'A ROLE FOR IFN-GAMMA IN ENHANCED BACTERIAL CLEARANCE OF PSEUDOMONAS-AERUGINOSA FROM THE LUNG FOLLOWING INTESTINAL IMMUNIZATION WITH KILLED BACTERIA', JOURNAL OF LEUKOCYTE BIOLOGY, 111-111 (1993) |
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1990 |
Husband A, Dunkley M, 'Helper T cell control of mucosal immune responses', Today's Life Science, 2 22-31 (1990)
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1990 |
DUNKLEY ML, HUSBAND AJ, UNDERDOWN BJ, 'COGNATE T-CELL HELP IN THE INDUCTION OF IGA RESPONSES INVIVO', IMMUNOLOGY, 71 16-19 (1990)
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1990 |
DUNKLEY ML, HUSBAND AJ, 'ROUTES OF PRIMING AND CHALLENGE FOR IGA ANTIBODY-CONTAINING CELL RESPONSES IN THE INTESTINE', IMMUNOLOGY LETTERS, 26 165-170 (1990)
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1990 |
Dunkley ML, Husband AJ, 'The role of non-B cells in localizing an IgA plasma cell response in the intestine', Regional Immunology, 3 336-340 (1990)
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1989 |
Dunkley ML, Husband AJ, 'Role of antigen in migration patterns of T cell subsets arising from gut-associated lymphoid tissue.', Regional immunology, 2 213-224 (1989)
Studies of the migration of antigen-specific regulatory T cell subsets responding to gut immunization were undertaken to clarify their migratory potential and the role of antigen ... [more]
Studies of the migration of antigen-specific regulatory T cell subsets responding to gut immunization were undertaken to clarify their migratory potential and the role of antigen in their localization. In initial experiments, lymphocytes collected from the thoracic duct of rats after immunization of Peyer's patches (PP) with keyhole limpet hemocyanin (KLH), were enriched for T helper (Th) cells and labelled with the fluorochrome H33342. In other experiments, a higher frequency of antigen-specific T cells was achieved by short-term culture of the enriched Th cells in the presence of KLH and the blast cells labelled with 3H-thymidine. The distribution of both populations was determined after injection into immunized and unimmunized syngeneic recipients. Whereas the uncultured population (predominantly small Th cells) localized almost exclusively in follicular lymphoid tissues, the cells expanded by secondary culture (predominantly Th blasts) appeared in the gut lamina propria (LP) initially, then in PP and mesenteric lymph nodes. The Th blasts in the LP were almost always seen in close proximity to the gut epithelium. However, the migration of neither population appeared to be influenced significantly by antigen, in contrast to previous findings with regard to IgA-committed B cells. The initial subepithelial location of Th blasts in the gut LP and their subsequent appearance in PP may provide a mechanism by which antigen presented by epithelial cells could influence B cell differentiation in PP through modulation of signals expressed by these T cells.
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1987 |
Dunkley ML, Husband AJ, 'Antigen-specific helper T cells in the intestine: origin and migration.', Advances in experimental medicine and biology, 216 A 119-130 (1987)
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1987 |
DUNKLEY ML, HUSBAND AJ, 'DISTRIBUTION AND FUNCTIONAL-CHARACTERISTICS OF ANTIGEN-SPECIFIC HELPER T-CELLS ARISING AFTER PEYER PATCH IMMUNIZATION', IMMUNOLOGY, 61 475-482 (1987)
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1986 |
DUNKLEY ML, HUSBAND AJ, 'THE INDUCTION AND MIGRATION OF ANTIGEN-SPECIFIC HELPER-CELLS FOR IGA RESPONSES IN THE INTESTINE', IMMUNOLOGY, 57 379-385 (1986)
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1985 |
DUNKLEY M, CRIPPS A, SCICCHITANO R, CLANCY R, 'RYE GRASS ALLERGEN INDUCED LYMPHOCYTE-PROLIFERATION', ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY, 3 77-83 (1985)
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1985 |
HUSBAND AJ, DUNKLEY ML, 'LACK OF SITE OF ORIGIN EFFECTS ON DISTRIBUTION OF IGA ANTIBODY-CONTAINING CELLS', IMMUNOLOGY, 54 215-221 (1985)
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1984 |
HUSBAND AJ, DUNKLEY ML, 'T-CELL REGULATION OF THE MUCOSAL IGA IMMUNE-RESPONSE', JOURNAL OF LEUKOCYTE BIOLOGY, 36 417-417 (1984) |
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1984 |
HUSBAND AJ, DUNKLEY ML, CRIPPS AW, CLANCY RL, 'ANTIGEN-SPECIFIC RESPONSE AMONG LYMPHOCYTES-T FOLLOWING INTESTINAL ADMINISTRATION OF ALLOANTIGENS', AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 62 687-699 (1984)
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1984 |
HUSBAND AJ, DUNKLEY ML, SCICCHITANO R, SHELDRAKE RF, 'INDUCTION AND DELIVERY OF MUCOSAL IMMUNE-RESPONSES', JOURNAL OF DENTAL RESEARCH, 63 465-469 (1984)
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1981 |
Russell PJ, Cunningham J, Dunkley M, Wilkinson NM, 'The role of suppressor T cells in the expression of autoimmune haemolytic anaemia in NZB mice', Clinical and Experimental Immunology, 45 496-503 (1981)
The course of haemolytic anaemia in NZB mice has been altered by injection of spleen cells from diseased mice into younger ones before the onset of clinical disease. Recipients gr... [more]
The course of haemolytic anaemia in NZB mice has been altered by injection of spleen cells from diseased mice into younger ones before the onset of clinical disease. Recipients greater than 6 weeks of age developed early-onset autoimmune disease; recipients less than 6 weeks of age recovered from early induced disease and showed a delay in the onset of spontaneous disease as compared with untreated NZB mice. This delay was due to the induction in the young mice of splenic suppressor cells. These cells were non-adherent to nylon wool and suppressed autoantibody formation on transfer to old Coombs-positive recipients. Suppressor cells active against autoantibody-producing cells may be present in young untreated NZB mice, but not in sufficient numbers to suppress autoantibody production on adoptive transfer to Coombs-positive recipients; however, when Ig-negative cells from the spleens of very young NZB mice were transferred together with Ig-positive cells from Coombs-positive donor mice to irradiated NZB recipients, the autoantibody production of the transferred B cells was suppressed in some cases. Suppressor cell activity could also be induced by co-culture of spleen cells from old Coombs-positive and young Coombs-negative NZB mice in vitro.
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1978 |
Shortman K, Dunkley M, Ryden A, 'Some requirements for a linear cell dose response in vitro assay for the T-cell progenitors of cytotoxic lymphocytes', Journal of Immunological Methods, 19 369-385 (1978)
To develop a precise assay for the T-cell progenitors of cytotoxic lymphocytes (CL-progenitors), lymphoid cells were cultured under optimal conditions in Marbrook vessels with mit... [more]
To develop a precise assay for the T-cell progenitors of cytotoxic lymphocytes (CL-progenitors), lymphoid cells were cultured under optimal conditions in Marbrook vessels with mitomycin-treated allogeneic stimulator cells, and the total level of CL produced 5 days later estimated by a modified 51Cr release assay. Conditions were adjusted so an arithmetically linear cell dose response relationship was obtained. Three aspects of the cell dose response curve required attention. (1) At low responding cell inputs a macrophage-like cell became limiting (despite the presence of allogeneic macrophages in the stimulating cell population), leading to a lag in the response. This limitation was overcome by adding a low level of irradiated syngeneic macrophages, or by using irradiated syngeneic spleen 'filler' cells. (2) The slope of the resultant linear dose response region could be reduced if desired by changing from cellophane dialysis membranes to 0.1 µ pore size nuclepore membranes, suggesting a stimulatory role for some higher molecular weight soluble factor produced in the cultures. (3) At higher responding cell inputs a marked and extensive plateu was obtained. CL developing early in the response appeared to be destroying the allogeneic stimulator cells causing the response to be self-limiting. This problem was overcome by using a responding cell concentration lower than commonly employed. Assays using mixed leukocyte cultures in the lag or plateau regions could give misleading values for CL-progenitor activity. It is suggested that some examples of apparent synergism in CL generation may have resulted from these effects, rather than T-cell helper T-cell progenitor interactions. © 1978.
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1977 |
Beverley PC, Feldmann M, Dunkley M, McKenzie I, 'Antigenic phenotypes of T-cell subsets.', Transplantation Proceedings, 9 703-704 (1977) |
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1977 |
Shortman K, Ryden A, Dunkley M, Von Boehmer H, 'Some requirements for the response of separated T-cell sub-populations to the mitogens phytohaemagglutinin and concanavalin A', Australian Journal of Experimental Biology and Medical Science, 55 585-603 (1977)
The proliferative response of various separated populations of mouse spleen and thymus lymphocytes to the mitogen phytohaemagglutinin (PHA) was not a direct function of the level ... [more]
The proliferative response of various separated populations of mouse spleen and thymus lymphocytes to the mitogen phytohaemagglutinin (PHA) was not a direct function of the level of responsive T cells, but was governed by other regulatory effects. These included a stimulation by adherent macrophages, an inhibition by a separate population of adherent cells and an adherent cell independent restriction of proliferation at high cell concentration. In contrast, the proliferative response to Concanavalin A (Con A) was more closely related to the level of responsive T cells. All density and electrophoretically isolated sub-sets of splenic T cells appeared capable of a proliferative response to PHA and Con A, although under some conditions the PHA responsiveness of certain fractions was suppressed. In the thymus, the minor low T subpopulation appeared capable of response to both mitogens, and accounted for all the activity of the unfractioned thymus cells. No response to either mitogen could be obtained from the major, high T thymocyte population.
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1976 |
Beverley PCL, Woody J, Dunkley M, Feldmann M, McKenzie I, 'Separation of suppressor and killer T cells by surface phenotype', Nature, 262 495-497 (1976)
AMONG thymus-derived (T) lymphocytes of the mouse, several functionally distinct subsets may be identified (for review, see ref. 1). Early studies have shown synergy in graft-vers... [more]
AMONG thymus-derived (T) lymphocytes of the mouse, several functionally distinct subsets may be identified (for review, see ref. 1). Early studies have shown synergy in graft-versus-host reactions of different populations of lymphoid cells2, and in vitro studies have demonstrated interactions between cells from anti-lymphocyte serum-treated mice (T1 cells) and adult thymectomised mice (T2 cells)3. A similar synergy has been observed in the generation of T helper and T suppressor cells in vitro4. Clearer definition of the subsets of T cells interacting in the induction of immune responses has come from the use of allo-antisera recognising differentiation antigens on T cells. In particular, the use of antisera to the Ly series of antigens5 has enabled the separation of amplifying (MLR) cells from killer cells6. Similarly in the humoral response helper T cells can be distinguished from suppressor T cells 7. In this report, we show that killer and suppressor T cells, both generated in vitro and carrying the Ly-2 and 3 antigens can also be separated using antisera to surface antigenic markers. We also present data suggesting that suppressor cells of similar phenotype may have an important function in vivo in the immune response. © 1976 Nature Publishing Group.
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1975 |
Feldmann M, Beverley PCL, Dunkley M, Kontiainen S, 'Different Ly antigen phenotypes of in vitro induced helper and suppressor cells', Nature, 258 614-616 (1975)
THYMUS-derived (T) cells have a major role in immune systems. They mediate various functions, such as T-B cooperation ("helper cells") 1 and the mixed lymphocyte reactio... [more]
THYMUS-derived (T) cells have a major role in immune systems. They mediate various functions, such as T-B cooperation ("helper cells") 1 and the mixed lymphocyte reaction2, become killer cells3, are active in graft versus host responses (reviewed in ref. 4) and act as suppressor cells5. The identification of the cells responsible for these functions as T cells was facilitated by the use of antisera against the T-cell-specific alloantigen, Thy-1 (ref. 6) (formerly known as ¿). It has been reported that Ly allo-antigens, present exclusively on T cells7, identify functionally distinct subpopulations of T cells8. For example, T helper cells were lysed by anti-Ly-1, but not by anti-Ly-2, so that their phenotype is Ly-1+2-, whereas T killer cells were a distinct subpopulation, being Ly-1-2 +. We report here that specific T suppressor cells induced in vitro have a different Ly alloantigen phenotype from T helper cells induced in vitro from the same spleen cell pool. © 1975 Nature Publishing Group.
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1974 |
Miller RG, Dunkley M, 'Quantitative analysis of the
Using 51Cr-labelled P-815 mastocytoma cells as target cells and CS7BL/6 spleen cells sensitized against DBA/2 antigens as effector cells, it is shown that the variation in the obs... [more]
Using 51Cr-labelled P-815 mastocytoma cells as target cells and CS7BL/6 spleen cells sensitized against DBA/2 antigens as effector cells, it is shown that the variation in the observed specific 51Cr release over a broad range of experimental conditions can be explained on the basis of a simple physical model of the interaction process. The model assumes that a target cell can be destroyed only after contact with an effector cell, contact takes place on a random basis, one contact is sufficient, and that one effector cell can kill several targets with unchanged efficiency. The fraction of target cells destroyed (f) depends only on the incubation time (t), the number of effector cells (n) and a constant interaction probability (d). Thus f = 1 - e-ndt. However, the experimental measurement, the fraction of 51Cr specifically released into the supernatant during the assay, may not be the same as the fraction of target cells destroyed because it takes considerable time for the releasable 51Cr to be released from a damaged target cell. This can be overcome experimentally by following the standard 37 °C incubation with a further incubation at 45 °C during which there are no new lytic events but all previously damaged target cells release the remainder of their releasable 51Cr. The model enables one to obtain accurate measurements of relative effector cell frequency over a broad range of experimental conditions. © 1974.
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1974 |
Dunkley M, Miller RG, Shortman K, 'A modified
An improved 51Cr release assay for cytotoxic lymphocytes has been developed. The assay system combines the technical advantages of a titration tray method with a modification whic... [more]
An improved 51Cr release assay for cytotoxic lymphocytes has been developed. The assay system combines the technical advantages of a titration tray method with a modification which enables a more quantitative measure of the cytotoxicity of sensitized cell preparations in a shorter time. A simple mathematical model describing the cytotoxic lymphocyte-target cell interaction has been shown to apply to this system. The advantages and limitations of the assay system are discussed and the recommended procedure is described in detail. © 1974.
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