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Role of adaptive immune cells in the anti‐colitic effect of helminth antigen‐pulsed dendritic cells (650.17)
Author(s) -
Matisz Chelsea,
Wang Arthur,
Sharkey Keith,
McKay Derek
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.650.17
Subject(s) - immune system , adoptive cell transfer , antigen , immunology , colitis , acquired immune system , dendritic cell , myeloperoxidase , interleukin 10 , biology , t cell , chemistry , inflammation
Role of adaptive immune cells in the anti‐colitic effect of helminth antigen‐pulsed dendritic cells Chelsea E. Matisz 1 , Arthur Wang 1 , Keith A. Sharkey 1 , Derek M. McKay 1 . Department of Physiology & Pharmacology, University of Calgary, AB, Canada. Helminth parasites have evolved as potent modulators of the host immune system. Epidemiological, experimental, and clinical trials report that infection with helminths can attenuate concomitant inflammatory disease. The role of dendritic cells (DC) in these protective immune responses has only recently been explored. The adoptive transfer of in vitro derived dendritic cells, when pulsed with antigens from the helminth Hymenolepis diminuta (HD), protect recipient mice against dinitrobenzene sulfonic acid (DNBS)‐induced colitis. The transfer of HD‐pulsed DCs (HD‐DC) is associated with reduced disease activity scores, colonic myeloperoxidase (MPO) activity, improved histology damage scores, and increased IL‐4 and IL‐10 in stimulated splenocytes compared to DNBS only controls. As these cytokines are indicative of Th2 responses, we assessed the role of adaptive immunity in the protective effect of HD‐DCs. DCs were generated in vitro , treated with HD antigen for 24 hours, and transferred (10 6 , ip) to wild type and RAG deficient mice, which lack T and B cells. DNBS colitis was induced 48 hours after cell transfer, and necropsies performed 3 days later. Significantly less DNBS‐induced disease was observed in WT animals treated with HD‐DCs, compared to RAG deficient mice treated with HD‐DCs (n=6‐12, 2 experiments; F( 2,39 )=8.45, p=0.001). HD‐DCs significantly suppressed colonic MPO in both WT and RAG deficient mice. These results suggest that while T and/or B cells are essential to the anti‐colitic clinical response driven by HD‐DC, they are not required for reduced granulocyte infiltration. Overall these experiments highlight the therapeutic value of helminth antigens, and their potential to program DCs to attenuate inflammatory disease.