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 (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.


CONCLUSIONS
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.
Maris
Charles H
CH
Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, Baltimore, MD 21231, USA. charlesmaris@gmail.com
Chappell
Craig P
CP
Jacob
Joshy
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016753:Interleukin-10