THE ABILITY OF TRANSFORMING GROWTH-FACTOR-BETA-1 TO PREFERENTIALLY INHIBIT THE INDUCTION OF CYTOTOXICITY IN HUMAN T-CELLS IS DETERMINED BY THE NATURE OF THE ACTIVATING SIGNALS

TGF-beta is held to be a general inhibitor of the immune system, able to prevent the development of certain differentiated functions, such a s the induction of LAK activity by IL-2. In the present study, the pot ential of TGF-beta 1 to inhibit anti-tumour responses was assessed by determining its relative effect on the proliferation and cytotoxicity of human T-cells, following activation by anti-CD3, anti-CD3 plus anti -CD28 or anti-CD3 plus IL-2. The results demonstrated that TGF-beta 1 inhibits the induction of cytotoxicity in human T-cells stimulated via CD3 or CD3 and CD28 (P<0.01), without significantly altering their pr oliferative responses. The cytotoxic response following costimulation with IL-2 was hardly altered while costimulation via CD28 was suscepti ble to suppression, suggesting that TGF-beta 1 action is affected by t he nature of the costimulatory signals.