T cell costimulatory pathways: blockade for autoimmunity.
The activation of T lymphocytes is thought to require at least two signals, one delivered by the T cell receptor (TCR) complex after antigen recognition, and one provided on engagement of costimulatory receptors. The B7-1/B7-2-CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4) and CD154-CD40 pathways have been shown to be crucial in regulating T cell activation and tolerance. Novel members of the B7-CD28 superfamily have recently been discovered and they seem to be particularly important for regulating the responses of previously activated T cells. Superimposition of inhibitory signals like those delivered by CTLA-4 and programmed death (PD)-1-PD-1-ligand (PD-L1) pathway leads to a complex network of positive and negative costimulatory signals, the integration of which modulates immune responses. Furthermore, expression of several B7 homologues on cells other than professional antigen-presenting cells (APCs), indicate new mechanisms for regulating T cell responses in peripheral tissues. This review focuses on our current understanding of the members of the B7-CD28 superfamily and discusses their therapeutic potential.
Najafian
Nader
N
Laboratory of Immunogenetics and Transplantation, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Khoury
Samia J
SJ
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018106:CD28 Antigens