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Interleukin-10 plays an early role in generating virus-specific T cell anergy
BACKGROUND: Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV(ARM)) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMV(Clone13), which causes functional inactivation of effector T cells...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1903364/ https://www.ncbi.nlm.nih.gov/pubmed/17570849 http://dx.doi.org/10.1186/1471-2172-8-8 |
Sumario: | BACKGROUND: Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV(ARM)) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMV(Clone13), which causes functional inactivation of effector T cells and viral persistence. The mechanism by which LCMV(Clone13 )suppresses the antiviral immune response and persists in its host is unknown. RESULTS: Here we demonstrate that infection with LCMV(Clone13), but not with LCMV(ARM), resulted in a steady increase in the serum levels of the immuno-inhibitory cytokine, IL-10. Blockade of IL-10 using neutralizing monoclonal antibody injections in LCMV(Clone13)-infected mice led to dramatically enhanced effector T cell responses at 8 days post-infection. Even though IL-10 blockade resulted in decreased viral titers, the generation and maintenance of memory T cells was still compromised. The functional inactivation of CD8(+ )T cells in IL-10-blocked, chronically infected mice 30 days post-infection was incomplete as potent CTL (cytotoxic T lymphocytes) could be generated by in vitro re-stimulation. IL-10 knockout mice showed a similar pattern of antiviral CD8 T cell responses: early antiviral T cells were dramatically increased and viral levels were decreased; however, CD8 T cells in IL-10 knockout mice were also eventually anergized and these mice became persistently infected. CONCLUSION: Our data suggest that IL-10 plays an early role in LCMV(Clone13)-induced tolerance, although other factors collaborate with IL-10 to induce virus-specific tolerance. |
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