Impaired Proliferation and Th1 Differentiation of CD4⁺ T Cells of SHPS-1 Mutant Mice

Abstract

Background & Aims : SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region. It is highly expressed on the surface of CD11c⁺ dendritic cells (DCs) and macrophages. We have recently shown that priming of CD4⁺ T cells by DCs is markedly impaired in mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region. We have now evaluated further the functions of CD4⁺ T cells derived from SHPS-1 mutant mice. Methods : The expression of cell surface molecules on CD4⁺ T cells was examined by flow cytometry. The proliferation of CD4⁺ T cells was measured by [³H] thymidine incorporation. Cytokine production by CD4⁺ T cells was measured by ELISA. Results : SHPS-1 is expressed at low level on CD4⁺ T cells of wild-type mice. The T cell receptor (TCR)-stimulated proliferation of CD4⁺ T cells from SHPS-1 mutant mice was markedly decreased, whereas the TCR-stimulated production of IL-2 and IFN-γ by these cells was markedly increased, compared with those apparent with wild-type cells. Differentiation of CD4⁺ T cells from SHPS-1 mutant mice into Th1 cells was also impaired. Conclusions : Present results suggest that SHPS-1 is essential for proper regulation of CD4⁺ T cell functions.