Lymphocytic choriomeningitis virus infection is associated with long-standing perturbation of LFA-1 expression on CD8+ T cells.
Flow cytometric analysis of splenocytes from mice infected with lymphocytic choriomeningitis virus revealed marked and long-standing up-regulation of LFA-1 expression on CD8+, but not on CD4+ T cells. Appearance of CD8+ T cells with a changed expression of adhesion molecules reflected polyclonal activation and expansion which was demonstrated not to depend on CD4+ T cells or their products. Cell sorting experiments defined virus-specific CTL to be included in this population (LFA-1hiMEL-14lo), but since about 80% of splenic CD8+ T cells have a changed phenotype, extensive bystander activation must take place; this is indicated also by the finding that CD8+LFA-1hi cells transiently express several markers of cellular activation, e.g. transferrin receptor, IL-2R alpha and beta. Analysis of cells from the cerebrospinal fluid of mice infected intracerebrally showed that virtually all T cells present belonged to the CD8+LFA-1hi subset and, correspondingly, the ligand ICAM-1 was found to be up-regulated on endothelial cells in the inflamed meninges. Preincubation of LCMV-primed donor splenocytes with anti-LFA-1 markedly inhibited the transfer of virus-specific delayed-type hypersensitivity to naive recipients. Together, these findings indicate that up-regulation of LFA-1 expression is a critical factor involved in directing activated CD8+ T cells to sites of viral infection.
Andersson
E C
EC
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Christensen
J P
JP
Scheynius
A
A
Marker
O
O
Thomsen
A R
AR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D019041:L-Selectin; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology*
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D019041:L-Selectin