C. Bartholdy et al., Migration of activated CD8(+) T lymphocytes to sites of viral infection does not require endothelial selectins, BLOOD, 95(4), 2000, pp. 1362-1369
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.