A role of L3T4+ antigen in the Con A response of regenerating splenic L3T4+ T cells after Cy treatment.
The role of L3T4 antigens in the concanavalin A (Con A) response of regenerating spleen cells (Cy-SCs) after cyclophosphamide (Cy) treatment was studied. Anti-L3T4 monoclonal antibodies (Mabs) markedly inhibited the Con A response of the regenerating Cy-SCs, which do not require Ia molecules expressed on accessory cells (ACs) for Con A activation. However, the Con A response of normal spleen cells (N-SCs), which do require Ia molecules on ACs, was not inhibited by the same Mabs, although the Con A response of N-SCs, as well as that of Cy-SCs, was demonstrated to be mediated by L3T4+ T cells. The optimal times for the inhibitory effect of anti-L3T4 Mab was 7 days after Cy treatment, when the number of spleen cells increased to a maximum following a regenerative phase. Its inhibitory effect was reduced by high concentrations of Con A, and was restricted to the early phase of the Con A response. A short time exposure of the Cy-SCs to the anti-L3T4 Mabs was sufficient to decrease the response to Con A. Our results cannot explain the hypothesis that the L3T4 molecule functions solely by interacting with non-polymorphic parts of Ia molecules on ACs. Taken together, these results and those of other groups of investigators suggest that Con A-induced T-cell activation may be mediated by at least two or more interaction mechanisms involving either Ia or L3T4 molecules. Firstly, normal L3T4+ T cells may mainly interact with Con A involving self Ia molecules on the ACs. The extent of this interaction is sufficient to induce T-cell activation, and then does not need another L3T4 molecule. Secondly, the regenerating L3T4+ T cells may usually interact with the cell surface antigens of other T cells, including L3T4+, by the binding of both cell surface molecules to Con A in the absence of ACs, and then transmit a signal for T-cell activation. Anti-L3T4 Mabs may exert inhibitory effects somewhere in this process.
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D003208:Concanavalin A; D003520:Cyclophosphamide