Alloantigen-Induced Enhancement and Suppression of Human Cytotoxic Lymphocyte Responses to Autologous Lymphoblastoid Cell Lines

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Abstract
In vitro sensitization of human lymphocytes to autologous lymphoblastoid cell lines (LCL) gives rise to cytotoxic lymphocytes capable of lysing autologous and allogeneic LCL cells. Allogeneic LCL cells were markedly less effective than autologous LCL cells in terms of generating lymphocytes capable of lysing autologous LCL cells. The addition of allogeneic LCL cells or allogeneic normal lymphocytes to a mixture of responding lymphocytes and x-irradiated autologous LCL cells suppressed the generation of cytotoxic lymphocytes against autologous LCL cells. Suppressor T [thymus-derived] cells generated in allogeneic mixed leukocyte culture (MLC) and supernatants from MLC likewise decreased the generation of cytotoxic lymphocytes to x-irradiated autologous LCL cells. Alloantigens suppress the generation of cytototoxicty to x-irradiated autologous LCL cells, which ordinarily induce strong cytotoxic responses. Allogeneic stimulating cells and supernatants from MLC enhanced cytotoxic responses to autologous UV light or extensively heat-treated LCL cells that induce weaker cytotoxic responses. Possible mechanisms whereby alloantigens enhance or suppress cytotoxic respones to autologous abnormal cells and implications of these findings are discussed.