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Role of interleukin‐4 in down‐regulation of contact sensitivity by γδ T cells from tolerized T‐cell receptor α −/− mice
Author(s) -
Marian Szczepanik,
W Ptak,
Philip W. Askenase
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00837.x
Subject(s) - antigen , t cell receptor , biology , t cell , cytotoxic t cell , adoptive cell transfer , microbiology and biotechnology , cd8 , cd28 , antigen presenting cell , major histocompatibility complex , il 2 receptor , immunology , immune system , in vitro , biochemistry
Contact sensitivity (CS) is a classical example of an in vivo T‐cell‐mediated immune response that is under regulation. Such down‐regulation can be mediated by αβ T cells in mice that are tolerized by prior exposure to high doses of antigen. In contrast, we demonstrated previously that such high‐dose antigen tolerance in T‐cell receptor (TCR) α −/− H‐2 d mice induced antigen‐specific, apparently major histocompatibility complex‐unrestricted, CD4 − CD8 − γδ T cells, that also could down‐regulate CS responses antigen‐specifically in vivo , and also inhibited in vitro production of IFN‐γ. In the present experiments we employed H‐2 b ‐deficient TCRα −/− and TCRβ −/− mice, owing to different molecular constructs than were used previously, and confirmed that tolerized γδ T cells in these different H‐2 b αβ TCR −/− mice down‐regulated CS. Thus, γδ T‐cell suppressor function was not limited to mice bearing a special transgenic TCRα −/− DNA construct. Furthermore, employing monoclonal antibody and complement depletion in vitro and adoptive transfer in vivo , characterized the phenotype of these γδ down‐regulatory T cells as: CD3 + , CD28 + , CD40‐ligand + , Fas + , FcγR + and NK1.1 − . Also, in vitro antigen desensitization of these trinitrophenyl (TNP)‐specific TCRγδ + down‐regulatory cells was achieved with soluble TNP‐bovine serum albumin (BSA), but not with oxazolone‐BSA, showing that these suppressive γδ T cells have antigen‐specific receptors. Moreover, employing monoclonal antibody blocking of γδ suppressors in vitro , and of recipients in vivo , we showed that interleukin‐4 (IL‐4) was involved in this down‐regulation of CS by γδ T cells, while IL‐10 and transforming growth factor‐β 2 were not. In summary, generation of antigen‐specific, double‐negative, γδ suppressor cells, by tolerance of high antigen doses in TCRα −/− mice, appears to be a general phenomenon, and IL‐4 production is involved in their down‐regulation of the T helper type 1 cells that mediate CS.