CD45RC+ CD4 T cell subsets are maintained in an unresponsive state by the persistence of transfusion-derived alloantigen.
The ability of preoperative blood transfusion to extend the survival of organ allografts is well known but poorly understood. To study this phenomenon, adult PVG (RT1c) rats were rendered tolerant of DA (RT1a) cardiac allografts by prior donor-specific blood transfusion (DST). We investigated the cellular basis of the transfusion effect by adoptively transferring CD4 T cell subsets, obtained from thoracic duct lymph of tolerant rats, into cardiac allografted athymic PVG nude recipients. Surprisingly, CD4 T cells from DST rats evoked acute rejection on adoptive transfer. Evidence indicated that CD8 T cells played no role in DST-induced tolerance. Analysis of CD4 T cell subsets, defined in the rat by mAb OX22 (anti-CD45RC), revealed an unusual pattern of responsiveness. CD45RC+ CD4 T cells (normally capable of inducing prompt rejection), when obtained from rats given a specific blood transfusion, were depleted of alloreactive cells and deficient at inducing rejection. In contrast, the CD45RC- subset (normally slow at evoking graft destruction) was highly active and ten-fold-enriched in its ability to induce rejection. Destruction of cardiac allografts by this latter subset was, however, completely inhibited by giving nude recipients a specific (but not a third-party) blood transfusion two weeks before heart grafting and cell transfer. Apparently, tolerance was maintained by residual elements of the prior blood transfusion that prevented the specific CD45RC- subset from regaining an alloaggressive capacity.
Yang
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CP
Immunology Research Group, School of Biological Sciences, University of Manchester, Medical School, United Kingdom.
McDonagh
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M
Bell
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EB
D000818:Animals; D001803:Blood Transfusion; D015704:CD4 Antigens / Q000032:analysis*; D006084:Graft Rejection; D006087:Graft vs Host Reaction; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D007519:Isoantigens / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis*; D051381:Rats; D011914:Rats, Inbred BN; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D007519:Isoantigens; D017493:Leukocyte Common Antigens