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Original Article

^a Department of Medicine, University of Pennsylvania,
^b Wistar Institute, Philadelphia, PA 19104
^c Institut Pasteur, Paris 75015, France
421 Curie Blvd., BRB II/III 753, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.215-573-7599215-573-2955

tlaufer{at}mail.med.upenn.edu

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-A_β^b mice, major histocompatibility complex (MHC) class II I-A^b expression is limited to thymic cortical epithelium and deletion by hematopoietic antigen-presenting cells does not occur. In H2-DM–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-A_β^b and H2-DM–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-A_β^b and H2-DM–deficient mice suggests that a subset of CD4⁺25⁺ T cells is subject to negative selection on hematopoietic antigen-presenting cells.

Key Words: autoimmune disease • self-tolerance • thymic development • IL-2 receptor chain (CD25) • suppressor T cells

M.S. Jordan's present address is The Abramson Family Cancer Research Institute, Dept. of Laboratory Medicine and Pathology, University of Pennsylvania, Philadelphia, PA 19104.

© 2001 The Rockefeller University Press

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This article has been cited by other articles:

• Chen, X., Fang, L., Song, S., Guo, T. B., Liu, A., Zhang, J. Z. (2009). Thymic Regulation of Autoimmune Disease by Accelerated Differentiation of Foxp3+ Regulatory T Cells through IL-7 Signaling Pathway. J. Immunol. 183: 6135-6144 [Abstract] [Full Text]  

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