Raising the BAR on T cell trafficking and T cell driven immune responses.

T cell migration into tissues is required for normal adaptive immune responses. The F-BAR domain-containing protein CIP4 interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4-/- mice had normal T and B lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center formation, despite an intact CD40L-CD40 axis. CIP4-/- mice had also impaired contact hypersensitivity (CHS) to haptens and their T cells failed to adoptively transfer CHS.  CIP4-/- T cells, but not B cells, homed poorly to lymphoid organs.  In addition, ovalbumin activated CD4+ effector T cells from CIP4-/-/OT-II mice migrated poorly to antigen challenged skin. CIP4-/- T cells exhibited normal rolling on endothelial E- and P-selectins and chemotaxis to SDF-1a in vitro, but impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1, and defective arrest and transmigration across murine endothelial cell monolayers under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-mediated adhesive events that are essential for normal recruitment of T cells to lymphoid and cutaneous sites of antigen driven immune reactions.