Reversal of chronic to resolved infection by IL-10 blockade is LCMV strain dependent.
Chronic viral infections lead to CD8(+) T-cell exhaustion, characterized by impaired cytokine secretion. The immune-regulatory cytokine IL-10 promotes chronicity of infection with lymphocytic choriomeningitis virus (LCMV) Clone 13, as absence of IL-10 or blocking of IL-10R during early LCMV Clone 13 infection results in viral clearance. Thus, treatment of humans suffering from chronic viral infections with IL-10 neutralizing or IL-10R blocking antibodies was proposed to boost virus-specific T-cell responses to enhance control or even clear the viral infection. Here we demonstrate that although CD4(+) and CD8(+) T cells can produce elevated levels of cytokines in IL-10(-/-) mice early after infection compared with WT mice, IL-10(-/-) mice cannot clear an infection with the quicker replicating LCMV strain Docile, eventually resulting in T-cell exhaustion. These data suggest that the success of IL-10 blockade to control chronic viral infections may critically depend on the virulence of the infecting strain.
Institute of Microbiology, ETH Zurich, Zurich, Switzerland. richter@micro.biol.ethz.ch
Kirsten
K
Richter
Guillaume
G
Perriard
Annette
A
Oxenius
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors; D014779:Virus Replication
D053701:Receptors, Interleukin-10; D016753:Interleukin-10