Alpha 4 integrin directs virus-activated CD8+ T cells to sites of infection.
This article examines the role of VLA-4 in directing lymphocytes to sites of viral infection using the murine lymphocytic choriomeningitis virus infection (LCMV) as the model system. This virus by itself induces little or no inflammation, but in most mouse/virus strain combinations a potent T cell response is induced, which is associated with marked CD8+ cell-mediated inflammation. Two expressions of LCMV-induced inflammation were studied: meningitis induced by intracerebral infection and adoptive transfer of virus-specific delayed-type hypersensitivity. Our previous studies have shown that LCMV infection results in the appearance of activated CD8+ cells with an increased expression of VLA-4. In this study we have compared various T cell high and low responder situations, and these experiments revealed that acute inflammation correlates directly with VLA-4 expression on splenic CD8+ cells. This correlation could be extended to CD4+ and B cells in chronically infected low responder DBA/2 mice. The vascular ligand for VLA-4, VCAM-1, was found to be up-regulated on endothelial cells in sites of inflammation. Finally, preincubation of virus-primed donor cells with mAb to VLA-4 completely blocked the ability to transfer virus-specific, delayed-type hypersensitivity when the donor cells were given i.v., but not when the cells were injected directly into the test site. Co-transfer of CD8-depleted cells with anti-VLA-4-blocked cells did not reveal any cooperation. Taken together, these results indicate that VLA-4 play a critical role in lymphocyte homing during systemic virus infections and are involved in directing virus-specific CD8+ effector cells to sites of infection.
Christensen
J P
JP
Institute of Medical Microbiology, University of Copenhagen, Denmark.
Andersson
E C
EC
Scheynius
A
A
Marker
O
O
Thomsen
A R
AR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007124:Immunoenzyme Techniques; D016219:Immunotherapy, Adoptive; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1