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Abnormal Th1 Cell Differentiation and IFN- Production in T Lymphocytes from Motheaten Viable Mice Mutant for Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase-1¹

Wen-Mei Yu^*,, Siying Wang, Achsah D. Keegan, Mark S. Williams and Cheng-Kui Qu^2,*,

Departments of ^* Hematopoiesis and Immunology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, and Department of Pathology, University of Maryland School of Medicine, Rockville, MD 20855; and Department of Pathophysiology, Anhui Medical University, Hefei, China

Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) plays an important role in T and B lymphocyte signaling; however, the function of SHP-1 in Th cell differentiation, in particular, the Th1 response, has not been defined. In this study, we provide evidence that SHP-1 phosphatase negatively regulates Th1 cell development and IFN- production. Compared with the wild-type control, anti-CD3-activated mouse T lymphocytes carrying the motheaten viable mutation in the SHP-1 gene produced a significantly increased amount of IFN- in the presence of IL-12. This increase was also seen at the basal level without IL-12 addition. Similarly, Th1 cell differentiation and proliferation of anti-CD3-activated SHP-1 mutant lymph node cells in the presence or absence of IL-12 were markedly enhanced, indicating a negative role for SHP-1 phosphatase in such lymphocyte activities. Interestingly, IL-12-induced activation of Jak2 and STAT4, critical components for IL-12-mediated cellular responses, was shortened or attenuated in mutant T cells. Together these results suggest that SHP-1 negatively regulates Th1 cell development and functions through a mechanism that is not directly related to IL-12 signaling.

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				I.-K. Park, L. D. Shultz, J. J. Letterio, and J. D. Gorham TGF-{beta}1 Inhibits T-bet Induction by IFN-{gamma} in Murine CD4+ T Cells through the Protein Tyrosine Phosphatase Src Homology Region 2 Domain-Containing Phosphatase-1 J. Immunol., November 1, 2005; 175(9): 5666 - 5674. [Abstract] [Full Text] [PDF]