Regulation of T cell migration and the immune response by phosphoinositide 3-kinase gamma.

Abstract

Efficient migration of leukocytes is essential to an optimal immune response. The goal of these studies was to determine the role of the PI3K isoform p110γ in T cell migration, activation and the immune response as a whole. Our studies revealed that naïve T cell migration in response to the constitutive chemokines CCL19 and CCL21 in vitro is minimally affected by the loss of p110γ, which correlates with the absence of trafficking defects of p110γ/- T cells into secondary lymphoid organs in vivo . In several models of in vitro activation, p110γ deficiency does not impair naïve T cell activation and proliferation nor does it impact OT-I T cell proliferation and effector cell differentiation in vivo in response to vaccinia virus challenge. In contrast to naïve T cell migration, p110γ plays an important role in CD8 effector T cell migration both in response to inflammatory chemoattractants in vitro and to the inflamed peritoneum following challenge with vaccinia virus. Furthermore, while wild-type mice efficiently cleared vaccinia virus at high viral doses, infection of p110γ/- mice resulted in visible illness and death less than a week after infection. In all, we conclude that p110γ is dispensable for constitutive migration of naïve T cells and subsequent activation and differentiation into effector CD8 T cells, but plays a central role in the migration of effector CD8 T cells into inflammatory sites and in the antiviral immune response.