T cell costimulatory blockade: new therapies for transplant rejection.
Optimal T cell responses occur when T cells receive both antigen-specific signals through the T cell receptor and non-antigen-specific costimulatory signals through accessory cell surface molecules. The best understood costimulatory receptor is CD28. Signals through the T cell receptor and CD28 cooperatively induce cytokine gene expression and promote T cell proliferation and survival. Negative signals delivered through a related cell surface receptor, cytotoxic T lymphocyte antigen (CTLA-4), act to terminate immune responses and are required for normal immune homeostasis. This article reviews T cell costimulation, including the CD28/CTLA-4 system and other potential costimulatory pathways (such as CD40/CD154), the role of these pathways in normal immune responses, and the potential for the inhibition of these pathways to induce transplantation tolerance.
Gudmundsdottir
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Department of Medicine, University of Pennsylvania, Philadelphia 19104-6100, USA.
Turka
L A
LA
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D016030:Kidney Transplantation / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D000943:Antigens, Differentiation; D018106:CD28 Antigens