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PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation in antigen-induced CD4+ T cells.

T cell activation requires the formation and maintenance of stable interactions between T cells and APCs. The formation of stable T cell-APC contacts depends on the activation of the integrin LFA-1 (CD11aCD18). Several positive regulators of LFA-1 activation downstream of proximal TCR signaling have been identified, including talin; however, negative regulators of LFA-1 activity remain largely unexplored. Extended isoform of phosphatidylinositol phosphate kinase type I γ (PIPKIγ90) is a member of the type I phosphatidylinositol phosphate kinase family that has been shown previously to modulate talin activation of integrins through production of phosphatidylinositol 4,5-bisphosphate and direct binding to talin. In this study, we show that PIPKIγ90 negatively regulates LFA-1-mediated adhesion and activation of T cells. Using CD4(+) T cells from PIPKIγ90-deficient mice, we show that CD4(+) T cells exhibit increased LFA-1-dependent adhesion to ICAM-1 and increased rates of T cell-APC conjugate formation with enhanced LFA-1 polarization at the synapse. In addition to increased adhesiveness, PIPKIγ90-deficient T cells exhibit increased proliferation both in vitro and in vivo and increased production of IFN-γ and IL-2. Together, these results demonstrate that PIPKIγ90 is a negative regulator of Ag-induced T cell adhesion and activation.

Pubmed ID: 20855869 RIS Download

Mesh terms: Animals | Antigen-Presenting Cells | CD4-Positive T-Lymphocytes | Cell Adhesion | Cell Proliferation | Cell Separation | Flow Cytometry | Fluorescent Antibody Technique | Immunoblotting | Intercellular Adhesion Molecule-1 | Lymphocyte Activation | Lymphocyte Function-Associated Antigen-1 | Mice | Mice, Knockout | Phosphotransferases (Alcohol Group Acceptor) | Reverse Transcriptase Polymerase Chain Reaction | Transduction, Genetic

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI068062
  • Agency: NCI NIH HHS, Id: R01 CA085862
  • Agency: NIGMS NIH HHS, Id: T32 GM008692

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