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LAT-mediated signaling in CD4+CD25+ regulatory T cell development.

Publication ,  Journal Article
Koonpaew, S; Shen, S; Flowers, L; Zhang, W
Published in: J Exp Med
January 23, 2006

Engagement of the T cell receptor for antigen (TCR) induces formation of signaling complexes mediated through the transmembrane adaptor protein, the linker for activation of T cells (LAT). LAT plays an important role in T cell development, activation, and homeostasis. A knock-in mutation at Tyr136, which is the phospholipase C (PLC)-gamma1-binding site in LAT, leads to a severe autoimmune disease in mice. In this study, we show that CD4+CD25+ T reg cells that expressed Foxp3 transcription factor were nearly absent in both thymus and peripheral lymphoid organs of LAT(Y136F) mice. This defect was not a result of the autoimmune environment as LAT(Y136F) T reg cells also failed to develop in healthy LAT-/- mice that received mixed wild-type and LAT(Y136F) bone marrow cells. Moreover, adoptive transfer of normal CD4+CD25+ T reg cells protected neonatal LAT(Y136F) mice from developing this disease. These T reg cells effectively controlled expansion of CD4+ T cells in LAT(Y136F) mice likely via granzymes and/or TGF-beta-mediated suppression. Furthermore, ectopic expression of Foxp3 conferred a suppressive function in LAT(Y136F) T cells. Our data indicate that the LAT-PLC-gamma1 interaction plays a critical role in Foxp3 expression and the development of CD4+CD25+ T reg cells.

Duke Scholars

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 23, 2006

Volume

203

Issue

1

Start / End Page

119 / 129

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphoproteins
  • Mice, Transgenic
  • Mice
  • Membrane Proteins
  • Immunology
  • Forkhead Transcription Factors
  • CD4-Positive T-Lymphocytes
 

Citation

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Koonpaew, S., Shen, S., Flowers, L., & Zhang, W. (2006). LAT-mediated signaling in CD4+CD25+ regulatory T cell development. J Exp Med, 203(1), 119–129. https://doi.org/10.1084/jem.20050903
Koonpaew, Surapong, Shudan Shen, Lawrence Flowers, and Weiguo Zhang. “LAT-mediated signaling in CD4+CD25+ regulatory T cell development.J Exp Med 203, no. 1 (January 23, 2006): 119–29. https://doi.org/10.1084/jem.20050903.
Koonpaew S, Shen S, Flowers L, Zhang W. LAT-mediated signaling in CD4+CD25+ regulatory T cell development. J Exp Med. 2006 Jan 23;203(1):119–29.
Koonpaew, Surapong, et al. “LAT-mediated signaling in CD4+CD25+ regulatory T cell development.J Exp Med, vol. 203, no. 1, Jan. 2006, pp. 119–29. Pubmed, doi:10.1084/jem.20050903.
Koonpaew S, Shen S, Flowers L, Zhang W. LAT-mediated signaling in CD4+CD25+ regulatory T cell development. J Exp Med. 2006 Jan 23;203(1):119–129.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 23, 2006

Volume

203

Issue

1

Start / End Page

119 / 129

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphoproteins
  • Mice, Transgenic
  • Mice
  • Membrane Proteins
  • Immunology
  • Forkhead Transcription Factors
  • CD4-Positive T-Lymphocytes