T cell migration to sites of inflammation is an essential step of an effective immune
response. T cell recruitment is enhanced by the recognition of their cognate antigen
presented by the endothelium and their retention in the tissue is controlled by resident
antigen presenting cells. Vav1 is a guanidine exchange factor for RhoGTPases that is
activated through TCR signalling and is important for the cytoskeletal re-arrangements
occurring during T cell activation and migration. In this study we have investigated the
role of Vav1 in the recruitment and retention of antigen-specific T cells to sites of
inflammation.
HY-specific Ab-restricted WT and Vav1-/- T cells were generated and fully
characterised for specificity and expression of migration-related markers. Vav1-/- T cells
showed defects in adhesion, migration in response to ICAM-1, CXCL12 and CXCL10
and increased migratory speed in in vitro assays. Despite displaying defective motility in
vitro, both constitutive migration and recruitment of Vav1-/- T cells to antigenic sites
occurred normally. However, retention of Vav-1-/- T cells into antigenic tissue was
profoundly impaired. This may be due to the inability by Vav-1-/- T cells to respond to
‘stop’ signals delivered by co-engagement of TCR and CD28. In contrast to recent
reports on wild type T cells, Vav1-/- T cell migration and retention to sites of
inflammation was not affected by engagement of the co-stimulatory molecule CD28,
suggesting that Vav-1 recruitment during CD28-mediated signalling is instrumental for
Vav-1-mediated regulation of T cell traffic