Foxp3+ CD25– CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion
Expression of the IL-2 receptor α chain (CD25) by peripheral CD4 T cells follows cellular activation. However, CD25 expression by CD4 cells is widely used as a marker to identify regulatory T cells (T R ), although cells with regulatory properties are also found in the CD4 + CD25 – subset. By using...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 11; pp. 4091 - 4096 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Acad Sciences
15.03.2005
National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Expression of the IL-2 receptor α chain (CD25) by peripheral CD4 T cells follows cellular activation. However, CD25 expression by CD4 cells is widely used as a marker to identify regulatory T cells (T R ), although cells with regulatory properties are also found in the CD4 + CD25 – subset. By using in vivo functional assays and Foxp3 expression as a faithful marker of T R differentiation, we have evaluated the requirements for CD25 expression by peripheral T R . We first show that in vivo depletion of CD25 + cells prevents the development of spontaneous encephalomyelitis in recombination-activating gene (RAG)-deficient anti-myelin basic protein T cell antigen receptor (TCR) transgenic mice, and allows disease induction in otherwise healthy RAG-competent transgenic mice. Similar treatment in normal thymectomized animals is followed by the fast recovery of a normal number of CD25 + T R . Consistently, Foxp3-expressing T R encompassed in the CD25 – cell population convert to CD25 + after homeostatic expansion and are selectable by IL-2 in vitro . Surface expression of CD25 on T R is controlled by the activity of conventional CD4 cells and is fully labile because it can be lost and regained without affecting the functional potential of the cells. These findings reveal that Foxp3-expressing CD25 – cells constitute a peripheral reservoir of differentiated T R , recruited to the CD25 + pool upon homeostatic expansion and/or activation. This analysis, together with the notion that physiological commitment of T R takes place exclusively in the thymus should help for the interpretation of experiments assessing peripheral T R differentiation from naive CD4 T cells, defined as CD25 – . homeostasis mice T lymphocyte |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 To whom correspondence should be addressed. E-mail: jocelyne@igc.gulbenkian.pt. Communicated by N. M. Le Douarin, Académie des Sciences de l'Institut de France, Paris, France, February 3, 2005 Present address: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294. Author contributions: S.Z., T.L.-C., I.C., and J.D. designed research; S.Z., T.L.-C., I.C., M.F.M.-F., M.R., and J.D. performed research; S.Z., T.L.-C., I.C., M.F.M.-F., and J.D. analyzed data; and S.Z., T.L.-C., and J.D. wrote the paper. Abbreviations: TR, regulatory T cells; RAG, recombination-activating gene; TCR, T cell antigen receptor; T/R– and T/R+, anti-myelin basic protein TCR transgenic mice homo- and heterozygous for a null mutation of the RAG-1 gene; Tx, thymectomized; EAE, experimental autoimmune encephalomyelitis; LN, lymph node; PE, phycoerythrin. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0408679102 |