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 as the induction of LAK activity by IL-2. In the present study, the potential 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 proliferative responses. The cytotoxic response following costimulation with IL-2 was hardly altered, while costimulation via CD28 was susceptible to suppression, suggesting that TGF-beta 1 action is affected by the nature of the costimulatory signals.
University of Glasgow, Department of Surgery, Glasgow Royal Infirmary, Scotland, UK.
J
J
Xie
G
G
Gallagher
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000906:Antibodies; D015703:Antigens, CD; D017252:CD3 Complex; D016212:Transforming Growth Factor beta