Infected CD8α⁻ dendritic cells are the predominant source of IL-10 during establishment of persistent viral infection

Interleukin-10 (IL-10) is an important factor involved in T-cell dysfunction during persistent viral infection. Although several factors can negatively regulate T-cell activity, targeting of the IL-10 pathway alone is sufficient to regenerate T-cell activity and increase viral control. How IL-10 med...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-08, Vol.109 (35), p.14116-14121
Main Authors: Ng, Cherie T, Oldstone, Michael B. A
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Biological Sciences
blood serum
bone marrow
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD8 Antigens - immunology
CD8 Antigens - metabolism
chimerism
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Exhaustion
Female
Humans
Infections
Interferon Type I - immunology
Interferon Type I - metabolism
interleukin-10
Interleukin-10 - genetics
Interleukin-10 - immunology
Interleukin-10 - metabolism
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - metabolism
Lymphocytic choriomeningitis virus - growth & development
Lymphocytic choriomeningitis virus - immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
mutants
Receptors
Signal Transduction - immunology
Spleen
T lymphocytes
Transplantation Chimera
Viral infections
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interleukin-10 (IL-10) is an important factor involved in T-cell dysfunction during persistent viral infection. Although several factors can negatively regulate T-cell activity, targeting of the IL-10 pathway alone is sufficient to regenerate T-cell activity and increase viral control. How IL-10 mediates these effects is unclear. Here, we investigated the cellular source of IL-10 necessary for establishing T-cell exhaustion and viral persistence, using IL-10 reporter mice (VertX), cell-type–specific IL-10 and IL-10 receptor deletion mice, and bone marrow chimeric mice. During establishment of viral persistence, the cellular subset with the most prevalent expression of IL-10 was CD8α ⁻CD4 ⁺ dendritic cells (DCs), which produced IL-10 with increasing kinetics until 9 d postinfection. After this time point, DCs exhibited a modest decline in percentage of IL-10 ⁺ cells whereas B cells and CD4 ⁺ T cells increased minimally. Further analysis of the DC population demonstrated that IL-10 was primarily expressed in infected DCs. These DCs were a notable source of IL-10 as mutant mice with a DC-specific deletion of IL-10 had significantly decreased serum levels. Interestingly, viral infection was not directly causative of IL-10 expression; rather, IL-10 production appeared to be linked to type I IFN signaling. Our findings further illuminate the contribution of DCs to the production of IL-10 and to viral persistence.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1211910109