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The src homology 2 domain-containing tyrosine phosphatase 2 regulates primary T-dependent immune responses and Th

Robert J Salmond1, Gregory Huyer, Anastasia Kotsoni

  • 1Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom. robert.salmond@bbsrc.ac.uk

Journal of Immunology (Baltimore, Md. : 1950)
|November 8, 2005
PubMed

Insights

Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) normally suppresses T cell differentiation into the Th2 phenotype. Inhibiting SHP2 in T cells increases activation markers and cytokine secretion, impairing B cell responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is crucial for development and growth factor signaling.
  • Its specific role within the immune system, particularly in T cells, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of SHP2 in T cell-mediated immunity.
  • To elucidate the impact of dominant-negative SHP2 expression specifically within T cells on immune responses.

Main Methods:

  • Generation of transgenic mice expressing a dominant-negative SHP2 (SHP2(CS)) specifically in T cells.
  • Analysis of T cell development, activation markers, cytokine production (IL-4, IL-5, IL-10), and B cell responses in SHP2(CS) mice.
  • Assessment of T cell receptor (TCR) and co-inhibitory receptor signaling pathways (CTLA-4, PD-1).

Main Results:

  • T cell development (positive and negative selection) was normal in SHP2(CS) mice.
  • SHP2(CS) T cells exhibited heightened activation markers and increased secretion of IL-4, IL-5, and IL-10 in vitro.
  • Aged SHP2(CS) mice showed elevated serum antibody levels, but primary T-dependent B cell responses were impaired.
  • TCR-induced Lck phosphorylation was defective, while CTLA-4 and PD-1 signaling remained unaffected.

Conclusions:

  • Wild-type SHP2 plays a critical role in suppressing the differentiation of T cells towards the Th2 phenotype.
  • SHP2 acts as a negative regulator of T cell activation and Th2 polarization, impacting adaptive immunity.

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