Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T Cells

• Published in: The Journal of experimental medicine Vol. 194; no. 4; pp. 427 - 438
• Main Authors: Bensinger, Steven J., Bandeira, Antonio, Jordan, Martha S., Caton, Andrew J., Laufer, Terri M.
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 20.08.2001
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; Epithelial Cells - immunology; Histocompatibility Antigens Class II - immunology; Mice; Mice, Inbred C57BL; Original; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.194.4.427

CD4+25+ T cells are a unique population of immunoregulatory T cells which are critical for the prevention of autoimmunity. To address the thymic selection of these cells we have used two models of attenuated thymic deletion. In K14-Aβb mice, major histocompatibility complex (MHC) class II I-Ab expression is limited to thymic cortical epithelium and deletion by hematopoietic antigen-presenting cells does not occur. In H2-DMα–deficient mice, MHC class II molecules contain a limited array of self-peptides resulting in inefficient clonal deletion. We find that CD4+25+ T cells are present in the thymus and periphery of K14-Aβb and H2-DMα–deficient mice and, like their wild-type counterparts, suppress the proliferation of cocultured CD4+25− effector T cells. In contrast, CD4+25+ T cells from MHC class II–deficient mice do not suppress responder CD4+ T cells in vitro or in vivo. Thus, development of regulatory CD4+25+ T cells is dependent on MHC class II-positive thymic cortical epithelium. Furthermore, analysis of the specificities of CD4+25+ T cells in K14-Aβb and H2-DMα–deficient mice suggests that a subset of CD4+25+ T cells is subject to negative selection on hematopoietic antigen-presenting cells.