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

Flow cytometric analysis of splenocytes from mice infected with lympho cytic choriomeningitis virus revealed marked and long-standing up-regu lation of LFA-1 expression on CD8(+), but not on CD4(+) T cells. Appea rance of CD8(+) T cells with a changed expression of adhesion molecule s reflected polyclonal activation and expansion which was demonstrated not to depend on CD4(+) T cells or their products. Cell sorting exper iments defined virus-specific CTL to be included in this population (L FA-1(hi)MEL-14(lo)), but since about 80% of splenic CD8(+) T cells hav e a changed phenotype, extensive bystander activation must take place; this is indicated also by the finding that CD8(+)LFA-1(hi) cells tran siently express several markers of cellular activation, e.g. transferr in receptor, IL-2R alpha and beta. Analysis of cells from the cerebros pinal fluid of mice infected intracerebrally showed that virtually all T cells present belonged to the CD8(+)LFA-1(hi) subset and, correspon dingly, the ligand ICAM-1 was found to be up-regulated on endothelial cells in the inflamed meninges. Preincubation of LCMV-primed donor spl enocytes with anti-LFA-1 markedly inhibited the transfer of virus-spec ific delayed-type hypersensitivity to naive recipients. Together, thes e findings indicate that up-regulation of LFA-1 expression is a critic al factor involved in directing activated CD8(+) T cells to sites of v iral infection.