Inflammation-induced effector CD4(+) T cell interstitial migration is alpha-(v) integrin dependent

Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues appears to be integrin-independent actin-myosin based, during inflammation changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that T cell interstitial motility was critically dependent on RGD-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to increased α(v) integrin expression on effector CD4(+) T cells. Using intravital multi-photon imaging, we found that CD4(+) T cell motility was dependent on α(v) expression. Selective α(v) blockade or knockdown arrested T(H)1 motility in the inflamed tissue and attenuated local effector function. These data show a context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity.