Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection

TY - JOUR

T1 - Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection

AU - Ørding Kauffmann, Susanne

AU - Thomsen, Allan Randrup

AU - Christensen, Jan Pravsgaard

N1 - Keywords: Animals; CD8-Positive T-Lymphocytes; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Memory; Integrin alpha1beta1; Integrin alpha4beta1; Lymphocytic choriomeningitis virus; Meningitis; Mice; Mice, Inbred BALB C; Mice, Knockout; T-Lymphocytes; Virus Diseases

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1111/j.1365-3083.2006.01744.x

DO - 10.1111/j.1365-3083.2006.01744.x

M3 - Journal article

C2 - 16623929

SN - 0301-6323

VL - 63

SP - 290

EP - 298

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

IS - 4

ER -