CD28-CD80/86 and CD40-CD40L Interactions Promote Thymic Tolerance by Regulating Medullary Epithelial Cell and Thymocyte Development.
Development and central tolerance of T lymphocytes in the thymus requires both TCR signals and collaboration with signals generated through costimulatory molecule interactions. In this review, we discuss the importance of CD28-CD80/86 and CD40-CD40L costimulatory interactions in promoting normal thymic development. This discussion includes roles in the generation of a normal thymic medulla, in the development of specific T-cells subsets, including iNKT and T regulatory cells, and in the generation of a tolerant mature T-cell repertoire. We discuss recent contributions to the understanding of CD28-CD80/86 and CD40-CD40L costimulatory interactions in thymic development, and we highlight the ways in which the many important roles mediated by these interactions collaborate to promote normal thymic development.
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Joy A
JA
Williams
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Xuguang
X
Tai
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Richard J
RJ
Hodes
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand