title: Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family.
abstract: Immune responses need to be controlled for optimal protective immunity and tolerance. Coinhibitory pathways in the B7-CD28 family provide critical inhibitory signals that regulate immune homeostasis and defense and protect tissue integrity. These coinhibitory signals limit the strength and duration of immune responses, thereby curbing immune-mediated tissue damage, regulating resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors and microbes that cause chronic infections can exploit these coinhibitory pathways to establish an immunosuppressive microenvironment, hindering their eradication. Advances in understanding T cell coinhibitory pathways have stimulated a new era of immunotherapy with effective drugs to treat cancer, autoimmune and infectious diseases, and transplant rejection. In this review we discuss the current knowledge of the mechanisms underlying the coinhibitory functions of pathways in the B7-CD28 family, the diverse functional consequences of these inhibitory signals on immune responses, and the overlapping and unique functions of these key immunoregulatory pathways.
authors.affiliation: Department of Microbiology and Immunobiology, and Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Schildberg
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Klein
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Department of Microbiology and Immunobiology, and Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA 02115, USA. Electronic address: arlene_sharpe@hms.harvard.edu.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D060887:B7 Antigens / Q000276:immunology / Q000378:metabolism*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D007239:Infections / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D060887:B7 Antigens; D018106:CD28 Antigens