IL-10 regulates early IL-12-mediated immune responses induced by the radiation-attenuated schistosome vaccine.
Radiation-attenuated (RA) schistosomes penetrate the host via the skin where they stimulate intense inflammatory reactions and the release of pro-inflammatory IL-12, important for T(h)1-type immune responses which are partially host protective. However, RA larvae also induce the secretion of regulatory IL-10. We now show that following vaccination of IL-12p40(-/-) mice, abundant IL-10 was produced by in vitro cultured skin biopsies between days 4 and 14, corresponding to the down-regulation of MHC II expression by cells in the dermis and cells that emigrate from the skin. In IL-10(-/-) mice, inflammation of the vaccination site was increased with larger numbers of IL-12p40(+), MHC II(+) and CD86(+) cells in the dermal exudate, and was associated with elevated levels of skin-derived IL-12p40 and IL-1beta. These changes in IL-10(-/-) mice were also reflected by an increased number of cells in the skin-draining lymph nodes (sdLN) and greater levels of lymphocyte proliferation. Moreover, such mice had increased numbers of CD4(+) sdLN cells that were CD25(+), CD28(+) or CD152(+) and accessory cells that were CD40(+) or MHC II(+). Finally, the secretion of IFN-gamma (and IL-12p40) by in vitro cultured sdLN cells was substantially raised in IL-10(-/-) mice, but much reduced in IL-12p40(-/-) mice, resulting in the development of highly polarized T(h)1 and T(h)2 cytokine profiles in the two groups of mice respectively. We conclude that IL-10 has an important role early in the regulation of IL-12-mediated priming of acquired immune responses, and effectively contains excessive dermal inflammation and prevents the development of highly polarized T(h)1-type responses.
Hogg
Karen G
KG
Department of Biology (Area 5), PO Box 373, University of York, York YO10 5YW, UK.
Kumkate
Supeecha
S
Mountford
Adrian P
AP
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D046508:Culture Techniques; D004431:Ear, External / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012550:Schistosoma mansoni / Q000276:immunology* / Q000528:radiation effects; D012867:Skin / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology*
D000941:Antigens; D015703:Antigens, CD; D051940:B7-2 Antigen; D015704:CD4 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D014613:Vaccines, Attenuated; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens