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The p110γ isoform of phosphatidylinositol 3‐kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites
Author(s) -
Thomas Molly S.,
Mitchell Jason S.,
DeNucci Christopher C.,
Martin Amanda L.,
Shimizu Yoji
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0807561
Subject(s) - biology , effector , phosphatidylinositol , gene isoform , microbiology and biotechnology , kinase , peripheral , inflammation , immunology , genetics , gene , medicine
The role of PI‐3K in leukocyte function has been studied extensively. However, the specific role of the p110γ isoform of PI‐ 3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110γ does not regulate antigen‐dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Naïve p110γ −/− CD4 lymphocytes are phenotypically identical to their wild‐type (WT) counterparts and do not exhibit any defects in TCR‐mediated calcium mobilization or Erk activation. In addition, p110γ‐deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen‐experienced, p110γ‐deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen‐activated, p110γ‐deficient CD4 T cells express P‐selectin ligand, β2 integrin, β1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired F‐actin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110γ regulates the migration of antigen‐experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.