LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION IS ASSOCIATED WITH LONG-STANDING PERTURBATION OF LFA-1 EXPRESSION ON CD8(+) T-CELLS

Flow cytometric analysis of splenocytes from mice infected with lymphocytic choriomeningitis virus revealed marked and long-standing up-regulation of LFA-1 expression on CD8(+), but not on CD4(+) T cells. Appearance of CD8(+) T cells with a changed expression of adhesion molecules reflected polyclonal activation and expansion which was demonstrated not to depend on CD4(+) T cells or their products. Cell sorting experiments defined virus-specific CTL to be included in this population (LFA-1(hi)MEL-14(lo)), but since about 80% of splenic CD8(+) T cells have a changed phenotype, extensive bystander activation must take place; this is indicated also by the finding that CD8(+)LFA-1(hi) cells transiently express several markers of cellular activation, e.g. transferrin receptor, IL-2R alpha and beta. Analysis of cells from the cerebrospinal fluid of mice infected intracerebrally showed that virtually all T cells present belonged to the CD8(+)LFA-1(hi) subset and, correspondingly, the ligand ICAM-1 was found to be up-regulated on endothelial cells in the inflamed meninges. Preincubation of LCMV-primed donor splenocytes with anti-LFA-1 markedly inhibited the transfer of virus-specific delayed-type hypersensitivity to naive recipients. Together, these findings indicate that up-regulation of LFA-1 expression is a critical factor involved in directing activated CD8(+) T cells to sites of viral infection.