Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection.
The T-cell response to lymphocytic choriomeningitis virus was studied in mice lacking very late antigen-1 (VLA-1). The generation of virus-specific effector T cells was unimpaired in VLA-1(-/-) mice. In the memory phase, VLA-1 deficiency did not influence the number of memory CD8(+) T cells or their distribution between lymphoid and nonlymphoid organs. Regarding a functional role of VLA-1, we found that intracerebral infection of both VLA-1(-/-) and wild-type (wt) mice resulted in lethal T-cell-mediated meningitis, and quantitative and qualitative analyses of the cellular exudate did not reveal any significant differences between the two strains. Expression of VLA-1 was also found to be redundant regarding the ability of effector T cells to eliminate virus from internal organs of i.v. infected mice. Using delayed-type hypersensitivity (DTH) assays to evaluate subdermal CD8(+) T-cell-mediated inflammation, no significant influence of VLA-1 was found either in the primary response or in the memory phase. However, alpha-VLA-4 antibody reduced the DTH-like reaction in VLA-1(-/-) mice to a higher degree than in wt mice, suggesting a synergistic effect of blocking both integrins. Taken together, the current findings indicate that the expression of VLA-1 is not pivotal for T-cell-mediated antiviral immunity to a systemic infection.
Kauffmann
S Ø
SØ
Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
Thomsen
A R
AR
Christensen
J P
JP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory; D039222:Integrin alpha1beta1 / Q000235:genetics / Q000276:immunology*; D039041:Integrin alpha4beta1 / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008581:Meningitis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology* / Q000473:pathology
D039222:Integrin alpha1beta1; D039041:Integrin alpha4beta1