CCR2(+) and CCR5(+) CD8(+) T cells increase during viral infection and migrate to sites of infection

Chemokines and their receptors play a critical role in the selective recrui tment of various leukocyte subsets. In this study, we correlated the expres sion of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV), which are prototypic of a noncytopathic and a cytopathic virus, respectively. infection of mice wi th either virus resulted in rapid activation and overlapping cerebral expre ssion of a number of chemokine genes. Infection with VSV i.c. causes a rapi dly lethal, T cell-independent encephalitis, and infection resulted in a dr amatic early up-regulation of chemokine gene expression. Similar marked up- regulation of chemokine expression was not seen until late after LCMV infec tion and required the presence of activated T cells. Cerebral CCR gene expr ession was dominated by CCR1, CCR2 and CCR5. However, despite a stronger in itial chemokine signal in VSV-infected mice, only LCMV-induced T cell-depen dent inflammation was found to be associated with substantially increased e xpression of CCR genes. Virus-activated CD8(+) T cells were found to expres s CCR2 and CCR5, whereas activated monocytes/macrophages expressed CCR1 in addition to CCR2 and CCR5. Together, these CCR profiles readily account for the CCR profile prominent during CD8(+)-dependent CNS inflammation.