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Commitment to the regulatory T cell lineage requires CARMA1 in the thymus but not in the periphery

Academic Article
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Overview

related to degree

  • Barnes, Michael, Ph.D. in Immunology & Genetics, Scripps Research , Joint graduate program with Oxford University 2004 - 2010

authors

  • Barnes, Michael
  • Krebs, P.
  • Harris, N.
  • Eidenschenk, C.
  • Gonzalez-Quintial, R.
  • Arnold, C. N.
  • Crozat, K.
  • Sovath, S.
  • Moresco, E. M.
  • Theofilopoulos, Argyrios
  • Beutler, Bruce
  • Hoebe, K.

publication date

  • 2009

journal

  • PLoS Biology  Journal

abstract

  • Regulatory T (T(reg)) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4(+) T cells in a cytokine dependent manner. T(reg) cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4(+)Foxp3(+) T(reg) cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient T(reg) cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFbeta) and interleukin-2 (IL-2). In vivo, a small peripheral T(reg) pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral T(reg) cells are a dynamic population that may expand to limit immunopathology or promote chronic infection.

subject areas

  • Animals
  • Autoimmune Diseases
  • CARD Signaling Adaptor Proteins
  • Cytokines
  • Cytomegalovirus Infections
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Interleukin-2
  • Mice
  • Point Mutation
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes, Regulatory
  • Thymus Gland
  • Transforming Growth Factor beta
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Identity

PubMed Central ID

  • PMC2650725

International Standard Serial Number (ISSN)

  • 1544-9173

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.1000051

PubMed ID

  • 19260764
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Additional Document Info

start page

  • e1000051

volume

  • 7

issue

  • 3

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