Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion.
Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 10(7) spleen cells plus 3 x 10(7) bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,Dd; Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of V beta 11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of V beta 11+ T cells terminated by 180 days after tolerance induction. V beta 11+ T cells, which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with V beta 11-specific mAb. Furthermore, the CTL activity against class I (Dd) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (Dd) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.
Tomita
Y
Y
Department of Immunology, Kyushu University, Fukuoka, Japan.
Nishimura
Y
Y
Harada
N
N
Eto
M
M
Ayukawa
K
K
Yoshikai
Y
Y
Nomoto
K
K
D000818:Animals; D002999:Clone Cells; D003520:Cyclophosphamide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015398:Signal Transduction; D016038:Skin Transplantation / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide