Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions.
The phenotypic expression of I-region determinants on cells producing and responding to MLR suppressor factor (MLR-TsF) was established in these studies. Alloantigen-activated MLR suppressor T cells (MLR-Ts), which produce MLR-TsF bearing gene products of the I-C subregion, were exposed to anti-I subregion sera and complement (C) before in vitro culture for MLR-TsF production. Suppressor activity was prevented by removal of cells bearing I-C determinants, whereas elimination of cells expressing I-A/B determinants had no effect. Interestingly, cytotoxic elimination of cells displaying I-J determinants also prevented MLR-TsF production. Admixture of anti-I-J and I-C antiserum-treated cells for MLR-TsF production failed to reconstitute suppressor activity, indicating that I-C and I-J gene products are expressed on a single population of cells critical to MLR suppression, rather than on distinct interacting subpopulations. Anti-I-C serum activity specific for I-C+ MLR-Ts was removed by adsorption with nylon wool-nonadherent splenic T cells and concanavalin A-activated thymocytes; adsorption with splenic B cells from anti-Thy-1,2 serum and C-treated spleen failed to remove relevant anti-I-C activity. These data suggest that regulatory I-C molecules, like I-J molecules, are preferentially expressed on T lymphocytes. Expression of I-C, or other I-region molecules on responder cell targets of MLR-TsF activity was also investigated. Responder cells were pretreated with anti-I subregion-specific sera in blocking or complement-dependent cytotoxic protocols before addition to MLR with MLR-TsF. Neither blocking nor the cytotoxic removal of cells bearing I-C or other I-region determinants from MLR responder populations interfered with MLR-TsF suppression. Because it has previously been demonstrated that MLR-TsF interacts optimally with activated, I-C syngeneic target cells, blocking and cytotoxic studies with anti-I subregion sera were also performed with responder cells activated by 24 h culture in MLR in the absence of MLR-TsF. Brief MLR-TsF pulse after antiserum treatment generated marked suppression regardless of blocking or absence of cells bearing serologically detected I-region determinants. I-C restricted suppression may thus be mediated not by interaction with I-C-bearing cells, but by target cells which exist in requisite association with populations of I-C+ cells.
D000818:Animals; D000939:Epitopes; D007165:Immunosuppression Therapy; D007519:Isoantigens / Q000235:genetics*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008807:Mice, Inbred BALB C / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000939:Epitopes; D007519:Isoantigens