Abnormal Th1 cell differentiation and IFN-gamma production in T lymphocytes from motheaten viable mice mutant for Src homology 2 domain-containing protein tyrosine phosphatase-1

• Published in: The Journal of immunology (1950) 2005-01, Vol.174 (2), p.1013-1019
• Main Authors: Yu, Wen-Mei, Wang, Siying, Keegan, Achsah D, Williams, Mark S, Qu, Cheng-Kui
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Proliferation; Cells, Cultured; Growth Inhibitors - genetics; Growth Inhibitors - physiology; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interleukin-12 - metabolism; Interleukin-12 - physiology; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Protein Phosphatase 1; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - physiology; Receptors, Interleukin - physiology; Receptors, Interleukin-12; Signal Transduction - immunology; src Homology Domains - genetics; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.2.1013

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-gamma 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-gamma 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.