Resolution of a chronic viral infection after interleukin-10 receptor blockade.
A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon gamma production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8alpha+ dendritic cell (DC) numbers declined early after infection, whereas CD8alpha- DC numbers were not affected. CD8alpha- DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10 priming by CD8alpha- DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.
Ejrnaes
Mette
M
Immune Regulation Lab - DI3, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Filippi
Christophe M
CM
Martinic
Marianne M
MM
Ling
Eleanor M
EM
Togher
Lisa M
LM
Crotty
Shane
S
von Herrath
Matthias G
MG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002908:Chronic Disease; D007106:Immune Sera / Q000008:administration & dosage; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007106:Immune Sera; D053701:Receptors, Interleukin-10; D016753:Interleukin-10