Role of genetic background in P selectin-dependent immune surveillance of the central nervous system.
Although the blood-brain barrier and blood cerebrospinal fluid barrier maintain the central nervous system (CNS) as an immunologically privileged site, T lymphocytes can migrate through unstimulated brain endothelium and epithelium to perform immune surveillance or initiate inflammation. Our prior results suggested that early CNS migration of a CD4 Th1 cell line was facilitated by P selectin (CD62P) in (PL/JxSJL/J)F1 mice. Here, quantitative analysis of migration 2 h following adoptive transfer of fluorescently labeled cells revealed a 53-72% decrease in activated splenocyte, CD4 Th1 and CD8 migration, but not CD4 Th2, in CD62P-deficient C57BL6/J mice. Immunohistochemistry revealed constitutive expression of CD62P within the meninges and choroid plexus epithelia in C57BL6/J and SJL/J, but not BALB/cJ, mice. Activated splenocyte migration was approximately three- to four-fold greater in SJL/J as compared to BALB/cJ mice. Anti-CD62P treatment normalized this difference. Based on these results, we hypothesize that genetically determined kinetics of immune surveillance may regulate the phenotype of subsequent CNS inflammation.
Carrithers
Michael D
MD
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-0811, USA. michael.carrithers@yale.edu
Visintin
Irene
I
Viret
Christophe
C
Janeway
Charles S
CS
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics* / Q000276:immunology; D002831:Choroid Plexus / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005838:Genotype; D007157:Immunologic Surveillance / Q000235:genetics* / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D008297:Male; D008578:Meninges / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation; D016378:Tissue Transplantation
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1