This article examines the role of
VLA-4 in directing lymphocytes to sites of
viral infection using the murine lymphocytic choriomeningitis virus
infection (LCMV) as the model system. This virus by itself induces little or no
inflammation, but in most mouse/virus strain combinations a potent T cell response is induced, which is associated with marked CD8+ cell-mediated
inflammation. Two expressions of LCMV-induced
inflammation were studied:
meningitis induced by intracerebral
infection and adoptive transfer of virus-specific delayed-type
hypersensitivity. Our previous studies have shown that LCMV
infection results in the appearance of activated CD8+ cells with an increased expression of
VLA-4. In this study we have compared various T cell high and low responder situations, and these experiments revealed that acute
inflammation correlates directly with
VLA-4 expression on splenic CD8+ cells. This correlation could be extended to CD4+ and B cells in chronically infected low responder DBA/2 mice. The vascular
ligand for
VLA-4,
VCAM-1, was found to be up-regulated on endothelial cells in sites of
inflammation. Finally, preincubation of virus-primed donor cells with mAb to
VLA-4 completely blocked the ability to transfer virus-specific, delayed-type
hypersensitivity when the donor cells were given i.v., but not when the cells were injected directly into the test site. Co-transfer of CD8-depleted cells with anti-VLA-4-blocked cells did not reveal any cooperation. Taken together, these results indicate that
VLA-4 play a critical role in lymphocyte homing during systemic
virus infections and are involved in directing virus-specific CD8+ effector cells to sites of
infection.