The Src-homology domain 2-bearing protein tyrosine phosphatase-1 inhibits antigen receptor-induced apoptosis of activated peripheral T cells

Jinyi Zhang, Ally-Khan Somani, Stephen Watt, Gordon B. Mills, Katherine A. Siminovitch

Research output: Contribution to journalArticle

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Abstract

Restimulation of Ag receptors on peripheral T lymphocytes induces tyrosine phosphorylation-based signaling cascades that evoke Fas ligand expression and induction of Fas-mediated programmed cell death. In view of the role for the Src homology domain 2-bearing protein tyrosine phosphatase- 1 (SHP-1) in modulating TCR signaling, we investigated the influence of SHP- 1 on TCR-mediated apoptosis by assaying the sensitivity of peripheral T cells from SHP-1-deficient viable motheaten (me(v)) mice to cell death following TCR restimulation. The results of these studies revealed me(v) peripheral T cells to be markedly more sensitive than wild-type cells to induction of cell death following TCR stimulation. By contrast, PMA/ionophore and anti-Fas Ab- induced apoptotic responses were no different in me(v) compared with wild- type activated cells. Enhanced apoptosis of TCR-restimulated me(v) lymphocytes was associated with marked increases in Fas ligand expression as compared with wild-type cells, but was almost abrogated in both me(v) and wild-type cells by Fas-Fc treatment. Thus, the increased sensitivity of me(v) T cells to apoptosis following TCR restimulation appears to reflect a TCR- driven phenomenon mediated through up-regulation of Fas-Fas ligand interaction and induction of the Fas signaling cascade. These findings, together with the hyperproliferative responses of me(v) peripheral T cells to initial TCR stimulation, indicate that SHP-1 modulation of TCR signaling translates to the inhibition of both T cell proliferation and activation and, as such, is likely to play a pivotal role in regulating the expansion of Ag- stimulated T cells during an immune response.

Original languageEnglish (US)
Pages (from-to)6359-6367
Number of pages9
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - Jun 1 1999
Externally publishedYes

Fingerprint

Protein Phosphatase 1
Antigen Receptors
Protein Tyrosine Phosphatases
src Homology Domains
Apoptosis
T-Lymphocytes
Fas Ligand Protein
Cell Death
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Ionophores
Tyrosine
Up-Regulation
Phosphorylation
Cell Proliferation
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

The Src-homology domain 2-bearing protein tyrosine phosphatase-1 inhibits antigen receptor-induced apoptosis of activated peripheral T cells. / Zhang, Jinyi; Somani, Ally-Khan; Watt, Stephen; Mills, Gordon B.; Siminovitch, Katherine A.

In: Journal of Immunology, Vol. 162, No. 11, 01.06.1999, p. 6359-6367.

Research output: Contribution to journalArticle

Zhang, Jinyi ; Somani, Ally-Khan ; Watt, Stephen ; Mills, Gordon B. ; Siminovitch, Katherine A. / The Src-homology domain 2-bearing protein tyrosine phosphatase-1 inhibits antigen receptor-induced apoptosis of activated peripheral T cells. In: Journal of Immunology. 1999 ; Vol. 162, No. 11. pp. 6359-6367.
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