title: W3/25+ T cells mediate the induction of immunologic unresponsiveness in enhanced rat recipients of cardiac allografts.
abstract: Cellular suppressor mechanisms developing during the induction of immunologic enhancement were studied in LEW rats immunized actively with BN spleen cells and passively with LEW anti-BN hyperimmune serum 11 and 10 days before receiving a (LEW X BN)F1 cardiac allograft, respectively. With this regimen, graft survival is prolonged from 7.4 +/- 0.5 days in unmodified, acutely rejecting hosts to 25 +/- 12 days in enhanced recipients, with one-third of the grafts surviving indefinitely. To test for suppressor capacities, 60 X 10(6) splenic T helper/inducer (W3/25+) and T suppressor/cytotoxic (OX8+) cells were adoptively transferred 7 and 14 days after transplantation either into unmodified syngeneic LEW animals that received (LEW X BN)F1 test grafts 24 hr later or into T cell-deprived B rats with indefinitely functioning heart transplants that were reconstituted with sensitized lymph node cells (100 X 10(6). W3/25+ T cells harvested on days 7 and 14 from enhanced recipients prolonged test graft survival in unmodified hosts (13.1 +/- 2.3 and 13.3 +/- 1.3 days, respectively, p less than 0.001) and delayed rejection in reconstituted B rats from 6.7 +/- 0.5 to 18.2 +/- 6.5 and 23.3 +/- 5.8 days, respectively (p less than 0.001). OX8+ and B lymphocytes had no suppressor activity. However, enzymatic stripping of the surfaces of W3/25+ cells abrogated suppressor function. Similarly, after i.p. treatment with cyclophosphamide, W3/25+ T cells lost their suppressor properties. Lack of donor specific but not third party alloaggressiveness was demonstrated by the profoundly diminished ability of W3/25+ lymphocytes from enhanced hosts to recreate rejection in nonreconstituted B rats, even when exogenous interleukin 2 was administered. After pronase treatment, however, W3/25+ T cells were capable of inducing immunoresponsiveness at a tempo similar to naive T helper cells (31.5 +/- 12.5 vs 32.8 +/- 7.9). Thus, the present studies provide evidence for the development of a specific W3/25+ suppressor cell in the induction of active and passive enhancement. Coincident abrogation of specific T effector alloaggressiveness is apparently mediated by surface-blocking factors.
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation; D006649:Histocompatibility Antigens / Q000276:immunology; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D006649:Histocompatibility Antigens