Late engagement of CD86 after influenza virus clearance promotes recovery in a FoxP3+ regulatory T cell dependent manner

Influenza A virus (IAV) infection in the respiratory tract triggers robust innate and adaptive immune responses, resulting in both virus clearance and lung inflammation and injury. After virus clearance, resolution of ongoing inflammation and tissue repair occur during a distinct recovery period. B7...

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Bibliographic Details
Published in:PLoS pathogens 2014-08, Vol.10 (8), p.e1004315-e1004315
Main Authors: Moser, Emily K, Hufford, Matthew M, Braciale, Thomas J
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
B7-2 Antigen - immunology
Biology and Life Sciences
Cytokines
Experiments
Flocculation
Flow Cytometry
Forkhead Transcription Factors - immunology
Immune system
Infections
Influenza A virus - immunology
Laboratories
Lymphocytes
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Orthomyxoviridae Infections - immunology
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Studies
T-Lymphocytes, Regulatory - immunology
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Summary:Influenza A virus (IAV) infection in the respiratory tract triggers robust innate and adaptive immune responses, resulting in both virus clearance and lung inflammation and injury. After virus clearance, resolution of ongoing inflammation and tissue repair occur during a distinct recovery period. B7 family co-stimulatory molecules such as CD80 and CD86 have important roles in modulating T cell activity during the initiation and effector stages of the host response to IAV infection, but their potential role during recovery and resolution of inflammation is unknown. We found that antibody-mediated CD86 blockade in vivo after virus clearance led to a delay in recovery, characterized by increased numbers of lung neutrophils and inflammatory cytokines in airways and lung interstitium, but no change in conventional IAV-specific T cell responses. However, CD86 blockade led to decreased numbers of FoxP3+ regulatory T cells (Tregs), and adoptive transfer of Tregs into αCD86 treated mice rescued the effect of the blockade, supporting a role for Tregs in promoting recovery after virus clearance. Specific depletion of Tregs late after infection mimicked the CD86 blockade phenotype, confirming a role for Tregs during recovery after virus clearance. Furthermore, we identified neutrophils as a target of Treg suppression since neutrophil depletion in Treg-depleted mice reduced excess inflammatory cytokines in the airways. These results demonstrate that Tregs, in a CD86 dependent mechanism, contribute to the resolution of disease after IAV infection, in part by suppressing neutrophil-driven cytokine release into the airways.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004315