Regulation of lymphocyte responses in cancer patients. I. Study of cell-surface gangliosides by cholera toxin and their induction of impaired activation.

The gangliosides compose a major portion of the surface membrane structure of the lymphocytes and their expression may relate with functional properties of different lymphocyte subpopulations. In the present study, the binding of the ganglioside GM1 to the human peripheral blood mononuclear cells (PBMC) and their effects on the lymphocyte function were examined. Cholera toxin (CT) was used as an indicator for detection of GM1 on the cell surface. It was shown that the exogenous GM1 binds to normal PBMC and inhibits proliferative responses in vitro by various mitogens (Con A, PHA, PWM). It was also revealed that more than 18 h is required to induce unresponsiveness of lymphocytes by preincubation with GM1, even though GM1 bound very rapidly (10-30 min) to lymphocytes. Some intracellular event may be needed to induce unresponsive state of the lymphocytes by GM1 binding. Moreover, the number of CT binding lymphocytes and the amount of CT bound to each cell showed to increase in the cancer patients. These results suggest that the increase of GM1 in the serum and the lymphocyte surface may be one of the mechanisms of suppressed lymphocyte responsiveness in the various pathological states especially in the cancer patients.