The p110γ isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites

The role of PI-3K in leukocyte function has been studied extensively. However, the specific role of the p110 gamma isoform of PI-3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110 gamma does not regulate antigen- dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Nai r ve p110 gamma(-/-) CD4 lymphocytes are phenotypically identical to their wildtype ( WT) counterparts and do not exhibit any defects in TCR- mediated calcium mobilization or Erk activation. In addition, p110 gamma- deficient CD4 OT. II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen- experienced, p110 gamma- deficient CD4 OT. II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen- activated, p110 gamma-deficient CD4 T cells express P- selectin ligand, beta 2 integrin, beta 1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired Factin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110 gamma regulates the migration of antigen- experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.