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 requirement for endothelial selectins in extravasation of leukocytes at sites of viral infection, with major emphasis on the recruitment of virus-specific T(C)1 cells. Lymphocytic choriomeningitis virus (LCMV)-induced meningitis was used as our primary experimental model. Additionally, localized subdermal inflammation and virus clearance in internal organs were analyzed during LCMV infection. The generation of CD8(+) effector T cells in infected mutants was unimpaired. Quantitative and qualitative analysis of the inflammatory exudate cells in intracerebrally infected mice gave identical results in all strains of mice. Expression of endothelial selectin was also found to be redundant regarding the ability of effector cells to eliminate virus in nonlymphoid organs. Concerning LCMV-induced footpad swelling, absent or marginal reduction was found in E/P-sel -/- mice, compared with wild-type mice after local challenge with virus or immunodominant viral MHC class I restricted 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-Ig 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. (Blood. 2000;95:1362-1369)
Bartholdy
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Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
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Thomsen
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D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016130:Immunophenotyping; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D019040:E-Selectin; D019007:P-Selectin; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1