Alloantigen-induced enhancement and suppression of human cytotoxic lymphocyte responses to autologous lymphoblastoid cell lines

Abstract

In vitro sensitization of human lymphocytes to autologous lymphoblastoid cell lines (LCL) has been shown to give rise to cytotoxic lymphocytes capable of lysing autologous as well as allogeneic LCL cells. However, allogeneic LCL cells were found to be 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. Furthermore, suppressor T cells generated in allogeneic mixed leucocyte culture (MLC) and supernatants from MLC likewise decreased the generation of cytotoxic lymphocytes to X-irradiated autologous LCL cells. In contrast to the findings that alloantigens suppress the generation of cytotoxicity of X-irradiated autologous LCL cells, which ordinarily induce strong cytotoxic responses, were the findings that allogeneic stimulating cells and supernatants from MLC enhanced cytotoxic responses to autologous ultraviolet light or extensively heat-treated LCL cells that induce weaker cytotoxic responses. The possible mechanisms whereby alloantigens enhance or suppress cytotoxic responses to autologous abnormal cells and the implications of these findings are discussed.