Migration of activated CD8(+) T lymphocytes to sites of viral infection does not require endothelial selectins

Using mice deficient of E-selectin and E/P-selectin, we have studied the re quirement for endothelia( selectins in extravasation of leukocytes at sites of viral infection, with major emphasis on the recruitment of virus-specif ic T(c)1 cells. Lymphocytic choriomeningitis virus (LCMV)-induced meningiti s was used as our primary experimental model. Additionally, localized subde rmal inflammation and virus clearance in internal organs were analyzed duri ng LCMV infection. The generation of CD8(+) effector T cells in infected mu tants was unimpaired, Quantitative and qualitative analysis of the inflamma tory exudate cells in intracerebrally infected mice gave identical results in all strains of mice. Expression of endothelial selectin was also found t o be redundant regarding the ability of effector cells to eliminate virus i n nonlymphoid organs. Concerning LCMV-induced footpad swelling, absent or m arginal reduction was found in E/P-sel -/- mice, compared with wild-type mi ce after local challenge with virus or immunodominant viral MHC class I res tricted peptide, respectively. Similar results were obtained after adoptive transfer of wild-type effector cells into E/P-sel -/- recipients, whereas footpad swelling was markedly decreased in P-sel/ICAM-1 -/- and ICAM-1 -/- recipients, LCMV-induced footpad swelling was completely inhibited in ICAM- deficient mice transfused with donor cell preincubated with soluble VCAM-1- lg chimeric protein. Taken together, the current findings strongly indicate that the migration of T(c)1 effector cells to sites of viral infection can proceed in the absence of endothelial selectins, whereas ligands of the Ig superfamily are critically involved in this process. (C) 2000 by The Ameri can Society of Hematology.