Soluble antigen-primed inducer T cells activate antigen-specific suppressor T cells in the absence of antigen-pulsed accessory cells: phenotypic definition of suppressor-inducer and suppressor-effector cells.
This study was undertaken to characterize interactions among human T cell subpopulations involved in the generation of suppressor T cells specific for a soluble antigen. Purified PPD-primed Leu-3+ cells, when co-cultured for 7 days with fresh autologous Leu-2+ cells, induced differentiation of Leu-2+ but not Leu-3+ cells into specific suppressor T cells, which subsequently inhibited the proliferative response of fresh Leu-3+ cells to PPD but not to tetanus toxoid or allogeneic non-T cells. The PPD-specific suppressor effect of activated Leu-2+ cells was not due to altered kinetics of the PPD response and also extended to the secondary response of PPD-primed Leu-3+ cells. Furthermore, only those Leu-2+ cells that lacked the 9.3 marker, an antigen present on the majority of T cells including the precursors of cytotoxic T cells, differentiated into suppressor T cells. To analyze the inducer population, fresh Leu-3+ cells were separated into Leu-3+,8- and Leu-3+,8+ subpopulations with anti-Leu-8 monoclonal antibody, activated with PPD, and then were examined for inducer function. Although both Leu-3+,8- and Leu-3+,8+ cells proliferated in response to PPD and upon activation expressed comparable amounts of HLA-DR (Ia) antigens, the Leu-3+,8+ subpopulation alone induced Leu-2+ cells to become suppressor-effectors in the absence of PPD-pulsed autologous non-T cells. Once activated, however, Leu-2+ suppressor cells inhibited the PPD response of both Leu-3+,8- and Leu-3+,8+ cells. These results indicate that antigen-primed Leu-3+,8+ inducer cells can directly activate Leu-2+, 9.3- precursors of antigen-specific suppressor T cells in the absence of antigen-pulsed autologous non-T cells.
D000942:Antigens, Bacterial / Q000276:immunology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D010641:Phenotype; D013234:Stem Cells / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D000942:Antigens, Bacterial; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D014373:Tuberculin