Correlation between lymphocyte-induced donor-specific tolerance and donor cell recirculation. Role of class I and class II major histocompatibility complex.
Intravenous infusion of mice with viable allogeneic lymphocytes can produce donor-specific enhancement of skin graft survival, but only if the injected lymphocytes can persist in the host's recirculating lymphocyte pool for at least 3 days. We have investigated the relative roles of class I and class II MHC for C57BL/6 mice infused with lymphoid cells from co-isogenic strains mutated at class I MHC (bm1) or class II MHC (bm12), and for A.TH lymphoid cells infused into C3H (class I different, class II identical) or A.TH (class II different, class I identical). Injected cells differing from the host at class I MHC, but not at class II MHC, can be rapidly removed by host natural immune mechanisms (probably NK cells). Persistence is favored if the injected cells also carry host class I MHC, i.e., tolerance is more readily induced by injecting F1 (A x B) into A rather than B into A, consistent with the "missing self" hypothesis of NK recognition, with class I MHC being the relevant self-marker. Injected cells differing from the host at class II MHC but not at class I MHC always persist for at least 3 days, even when class I-different cells are being actively removed.
Sheng-Tanner
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XF
Ontario Cancer Institute, University of Toronto, Canada.
Miller
R G
RG
D000818:Animals; D002470:Cell Survival / Q000276:immunology; D005260:Female; D006082:Graft Enhancement, Immunologic; D006087:Graft vs Host Reaction; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D007108:Immune Tolerance / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016038:Skin Transplantation / Q000276:immunology; D014019:Tissue Donors
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II