IL-10 restricts memory T cell inflation during cytomegalovirus infection.
The beta-herpesvirus CMV induces a substantial and progressive expansion of virus-specific memory CD8 T cells, which protect the host against viral reactivation from latency. In this paper, we report that this expansion, or "inflation," of memory T cells is amplified dramatically during mouse CMV infection of IL-10 knockout (IL-10(-/-)) mice. T cells from IL-10(-/-) mice were oligoclonal, exhibited a highly activated phenotype, expressed antiviral cytokines, and degranulated in response to cognate Ag encounter ex vivo. Moreover, latent viral load was reduced in IL-10(-/-) mice. Importantly, these results were recapitulated by IL-10R blockade during chronic/latent infection of wild-type mice. These data demonstrate that regulatory immune mechanisms can influence CMV-specific T cell memory and suggest a possible rationale for the acquisition of functional IL-10 orthologs by herpesviruses.
Jones
Morgan
M
Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Ladell
Kristin
K
Wynn
Katherine K
KK
Stacey
Maria A
MA
Quigley
Máire F
MF
Gostick
Emma
E
Price
David A
DA
Humphreys
Ian R
IR
D000595:Amino Acid Sequence; D000818:Animals; D041702:BALB 3T3 Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology*; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D017735:Virus Latency / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D016753:Interleukin-10