Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens.
In light of the widely accepted view that Ia-restricted L3T4+ T helper cells play a decisive role in controlling the differentiation of Lyt-2+ cells, experiments were designed to examine whether Lyt-2+ cells can respond to antigen in the absence of L3T4+ cells. The results showed that highly purified Lyt-2+ cells gave high primary mixed lymphocyte reactions (MLR) to various class I differences, including both mutant and allelic differences; responses to class II (Ia) differences were generally undetectable with Lyt-2+ cells. The intensity of MLR to class I differences was not affected by addition of anti-L3T4 monoclonal antibodies (mAb) to the cultures or by removing T cells from the stimulator populations. Negative selection experiments showed that Lyt-2+ cells could respond to class I differences across Ia barriers. MLR of purified Lyt-2+ cells peaked on days 3-4 and then fell sharply; background responses with syngeneic stimulators (auto-MLR) were virtually absent. Parallel experiments with purified L3T4+ cells showed that this subset responded in MLR only to class II (Ia) and not class I differences, reached peak responses only on day 6 rather than days 3-4, and often gave high auto-MLR. Within the first 3-4 d of culture, MLR were generally higher with Lyt-2+ cells than L3T4+ cells. Although no evidence could be found that Ia-restricted L3T4+ cells were required for the response of Lyt-2+ cells, presentation of antigen by Ia+ cells appeared to be essential. Thus, responses were ablated by pretreating stimulator cells with anti-Ia mAb plus C'. Significantly the failure of Lyt-2+ cells to respond to anti-Ia plus C'-treated stimulators could not be restored by adding syngeneic spleen cells; addition of IL-2 led to only a minor (15%) restoration of the response. It is suggested that Ia+ cells provide an obligatory second signal required by Lyt-2+ cells.
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Schaefer
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001667:Binding, Competitive; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1