A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis.
Previous studies have shown that the chronic inflammation observed in the colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4+ Th1 T cells and is dependent on the presence of IFN-gamma for its initial development. As CD4+ T cells from IL-10(-/-) mice will cause colitis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered the possibility that the recipients' NK cells could be an important source of IFN-gamma for the development of colitis. Therefore, the ability of IL-10(-/-) CD4+ T cells to cause colitis in Rag-deficient recipients that had been depleted of NK cells was tested. Contrary to our expectations, NK cell-depleted recipients of IL-10(-/-) CD4+ T cells developed accelerated disease compared with nondepleted recipients. Furthermore, CD4+ T cells from normal mice (IL-10(+/+)) also caused colitis in NK cell-depleted recipient mice, but not in nondepleted recipients. NK cells inhibited effector CD4+CD45RBhigh T cells, and subsequent experiments showed that this effect was dependent on perforin. Thus NK cells can play an important role in down-regulating Thl-mediated colitis by controlling the responses of effector T cells to gut bacteria.
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA. fort@dnax.org
M M
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Fort
M W
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Leach
D M
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Rennick
D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D016654:Genes, RAG-1 / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000235:genetics; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
D015704:CD4 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D016753:Interleukin-10; D017493:Leukocyte Common Antigens