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Existence of T cells manifesting self-reactivity indistinguishable from alloreactivity
The studies reported here were designed to analyze the phenotypic characteristics of self-reactive T lymphocytes induced in culture by allogeneic effect factor (AEF), as well as the control of their functional activities by the major histocompatibility complex (MHC). Unprimed T cells cultured with AEF in the absence of exogenous stimulating target cells become activated against self-antigens, as evidenced by their ability to manifest two distinct activities. First, such cells could lyse syngeneic target cells. This cytolytic activity was directed against H-2K antigens and was mediated by Lyt-2+ T cells. Second, the AEF-activated T cells could be stimulated in a secondary culture to high levels of proliferative activity by irradiated syngeneic spleen cells. The stimulator cells in this syngeneic mixed lymphocyte reaction (MLR) were found to be Thy-1-negative, Ia-positive splenic adherent cells. Stimulation in the secondary syngeneic MLR was provided by I-region specificities, and the majority of the proliferating cells were Lyt-1+ cells. Finally, AEF-induced T cells were effective in serving as effectors of graft-vs-host reactions in vivo in syngeneic recipients. These results prove that, under appropriate conditions, murine T lymphocytes can display aggressive patterns of self-reactivity that are similar in both quantity and quality to the classical patterns of alloreactivity and may have great significance for our understanding of MHC recognition processes.
The studies reported here were designed to analyze the phenotypic characteristics of self-reactive T lymphocytes induced in culture by allogeneic effect factor (AEF), as well as the control of their functional activities by the major histocompatibility complex (MHC). Unprimed T cells cultured with AEF in the absence of exogenous stimulating target cells become activated against self-antigens, as evidenced by their ability to manifest two distinct activities. First, such cells could lyse syngeneic target cells. This cytolytic activity was directed against H-2K antigens and was mediated by Lyt-2+ T cells. Second, the AEF-activated T cells could be stimulated in a secondary culture to high levels of proliferative activity by irradiated syngeneic spleen cells. The stimulator cells in this syngeneic mixed lymphocyte reaction (MLR) were found to be Thy-1-negative, Ia-positive splenic adherent cells. Stimulation in the secondary syngeneic MLR was provided by I-region specificities, and the majority of the proliferating cells were Lyt-1+ cells. Finally, AEF-induced T cells were effective in serving as effectors of graft-vs-host reactions in vivo in syngeneic recipients. These results prove that, under appropriate conditions, murine T lymphocytes can display aggressive patterns of self-reactivity that are similar in both quantity and quality to the classical patterns of alloreactivity and may have great significance for our understanding of MHC recognition processes.