The Journal of Experimental Medicine
CSHL 2010 Immunology Conference
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Published online 20 August 2001. doi:10.1084/jem.194.4.427
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© The Rockefeller University Press, 0022-1007/2001/8/427/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 4, August 20, 2001 427-438

Original Article

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

Steven J. Bensingera, Antonio Bandeirac, Martha S. Jordanb, Andrew J. Catonb, and Terri M. Laufera

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-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-DM{alpha}–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-DM{alpha}–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-DM{alpha}–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 {alpha} chain (CD25) • suppressor T cells

Abbreviations used in this paper: 3dTx, thymectomized on day 3 of life; DP, double positive; IBD, inflammatory bowel syndrome; Rag-2°, recombination activating gene 2–deficient; SP, single positive.

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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