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Author Notes:
Joshy Jacob: jjacob3@emory.edu
CHM conceived and designed the study.
CHM and CPC carried out all experiments.
JJ participated in the design of the study and assisted CHM in writing the manuscript.
We thank Karin Smith for mouse colony management, Huming Hon, Guido Silvestri, Alp Oran and Joseph D. Miller for critically reading the manuscript and John Altman, Rafi Ahmed, and Matthias von Herrath for helpful advice.
Subjects:
Interleukin-10 plays an early role in generating virus-specific T cell anergy
Abstract:
Background
Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMVARM) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMVClone13, which causes functional inactivation of effector T cells and viral persistence. The mechanism by which LCMVClone13 suppresses the antiviral immune response and persists in its host is unknown.
Results
Here we demonstrate that infection with LCMVClone13, but not with LCMVARM, 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 LCMVClone13-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 LCMVClone13-induced tolerance, although other factors collaborate with IL-10 to induce virus-specific tolerance.
Copyright information:
© 2007 Maris et al; licensee BioMed Central Ltd.
This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).
