Regulation of cytotoxic T-lymphocyte activation by L-lactate and pyruvate.

The activation of cytotoxic T lymphocytes (CTL) in vivo was found to be strongly augmented by two injections of 0.2 ml 1 X 10(-1) M pyruvate in spite of the relatively high concentration of glucose (approximately 10(-2) M) in the blood. The repeated injection of 1 X 10(-1) M L-lactate, in contrast, was found to suppress cytotoxic responses in vivo. The activation of CTL and DNA synthesis in mixed lymphocyte cultures, on the other hand, was found to be suppressed by pyruvate (1 X 10(-2) M), and was substantially augmented by 1 X 10(-2) M L-lactate. The glucose concentration in the culture medium was also approximately 10(-2) M. Taken together, these results suggest that the utilization of glucose is relatively ineffective and that the respiratory metabolism is a more effective source of energy during the early T cell activation. The results suggest also that the aerobic glycolysis of macrophages and their release of L-lactate may contribute to their function as accessory cells in immune responses. The differences between the in vivo and in vitro results are discussed.