Journal of Leukocyte Biology eBioscience full spectrum cell analysis
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Originally published online as doi:10.1189/jlb.0807561 on June 3, 2008

Published online before print June 3, 2008
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(Journal of Leukocyte Biology. 2008;84:814-823.)
© 2008 by Society for Leukocyte Biology

The p110{gamma} isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites

Molly S. Thomas, Jason S. Mitchell, Christopher C. DeNucci, Amanda L. Martin and Yoji Shimizu1

Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota, USA

1 Correspondence: University of Minnesota Medical School, 6-112 Hasselmo Hall, 312 Church St., SE, Minneapolis, MN 55455, USA. E-mail: shimi002{at}umn.edu

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. Naïve p110{gamma}–/– 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, 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, 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 p110{gamma} regulates the migration of antigen-experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.

Key Words: inflammation • chemokines • leukocyte • activation • trafficking






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