Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection

Jinyi Zhang, Ally-Khan Somani, Darren Yuen, Ye Yang, Paul E. Love, Katherine A. Siminovitch

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The selection events shaping T cell development in the thymus represent the outcome of TCR-driven intracellular signaling cascades evoked by Ag receptor interaction with cognate ligand. In view of data indicating TCR- evoked thymocyte proliferation to be negatively modulated by the SHP-1 tyrosine phosphatase, a potential role for SHP-1 in regulating selection processes was investigated by analysis of T cell development in H-Y TCR transgenic mice rendered SHP-1 deficient by introduction of the viable motheaten mutation or a dominant negative SHP-1-encoding transgene. Characterization of thymocyte and peripheral T cell populations in H-Y TCR- viable motheaten mice revealed TCR-evoked proliferation as well as the positive and negative selection of H-Y-specific thymocytes to be enhanced in these mice, thus implicating SHP-1 in the negative regulation of each of these processes. T cell selection processes were also augmented in H-Y TCR mice carrying a transgene driving lymphoid-restricted expression of a catalytically inert, dominant-negative form of SHP-1. SHP-1-negative effects on thymocyte TCR signaling were not influenced by co-cross-linking of the CD28 costimulatory and/or CTLA-4 inhibitory receptors and appear, accordingly, to be realized independently of these comodulators. These observations indicate that SHP-1 raises the signaling threshold required for both positive and negative selection and reveal the inhibitory effects of SHP-1 on TCR signaling to be cell autonomous. The demonstrated capacity for SHP-1 to inhibit TCR-evoked proliferation and selection indicate SHP-1 modulatory effects on the magnitude of TCR-generated signal to be a key factor in determining the cellular consequences of TCR-ligand interaction.

Original languageEnglish (US)
Pages (from-to)3012-3021
Number of pages10
JournalJournal of Immunology
Volume163
Issue number6
StatePublished - Sep 15 1999
Externally publishedYes

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Non-Receptor Type 6 Protein Tyrosine Phosphatase
Thymocytes
T-Lymphocytes
Transgenes
Ligands
Thymus Gland
Transgenic Mice
Mutation
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Zhang, J., Somani, A-K., Yuen, D., Yang, Y., Love, P. E., & Siminovitch, K. A. (1999). Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection. Journal of Immunology, 163(6), 3012-3021.

Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection. / Zhang, Jinyi; Somani, Ally-Khan; Yuen, Darren; Yang, Ye; Love, Paul E.; Siminovitch, Katherine A.

In: Journal of Immunology, Vol. 163, No. 6, 15.09.1999, p. 3012-3021.

Research output: Contribution to journalArticle

Zhang, J, Somani, A-K, Yuen, D, Yang, Y, Love, PE & Siminovitch, KA 1999, 'Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection', Journal of Immunology, vol. 163, no. 6, pp. 3012-3021.
Zhang J, Somani A-K, Yuen D, Yang Y, Love PE, Siminovitch KA. Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection. Journal of Immunology. 1999 Sep 15;163(6):3012-3021.
Zhang, Jinyi ; Somani, Ally-Khan ; Yuen, Darren ; Yang, Ye ; Love, Paul E. ; Siminovitch, Katherine A. / Involvement of the SHP-1 tyrosine phosphatase in regulation of T cell selection. In: Journal of Immunology. 1999 ; Vol. 163, No. 6. pp. 3012-3021.
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