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MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells¹

Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115

It has been known for decades that circulating human CD4 cells can express functional MHC class II molecules that induce T cell nonresponsiveness with Ag presentation. Because there is significant expression of MHC class II (MHC-II) determinants (DR) on a subpopulation CD4⁺CD25^high regulatory T cells (Treg), we examined the function of CD4 cells expressing MHC-DR. We demonstrate that MHC-II expression on human CD4⁺CD25^high T cells identifies a functionally distinct population of Treg that induces early contact-dependent suppression that is associated with high Foxp3 expression. In striking contrast, MHC-II^– CD4⁺CD25^high Treg induce early IL-4 and IL-10 secretion and a late Foxp3-associated contact-dependent suppression. The DR expressing CD25^high Treg express higher levels of Foxp3 message and protein, compared with the DR^–CD25^high Treg population. Direct single-cell cloning of CD4⁺CD25^high Treg revealed that, regardless of initial DR expression, ex vivo expression of CD25^high, and not DR, predicted which clones would exhibit contact-dependent suppression, high levels of Foxp3 message, and an increased propensity to become constitutive for DR expression. Thus, the direct ex vivo expression of MHC-II in the context of CD25^high identifies a mature, functionally distinct regulatory T cell population involved in contact-dependent in vitro suppression.

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				M. Swiatek-de Lange, W. Rist, H. F. Stahl, A. Weith, and M. C. Lenter Comment on "MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells" J. Immunol., March 15, 2008; 180(6): 3625 - 3625. [Full Text] [PDF]

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