Journal article
Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection
The Journal of immunology (1950), Vol.185(4), pp.2382-2392
08/15/2010
DOI: 10.4049/jimmunol.1000423
PMCID: PMC2923480
PMID: 20639494
Abstract
Regulatory Foxp3(+) CD4 T cells (Tregs) prevent spontaneous inflammation in the lungs, inhibit allergic and asthmatic responses, and contribute to tolerance to inhaled allergens. Additionally, Tregs have previously been shown to suppress the CD8 T cell response during persistent virus infections. However, little is known concerning the role that Tregs play in modulating the adaptive immune response during acute respiratory virus infections. We show following acute respiratory syncytial virus (RSV) infection that Foxp3(+) CD4 Tregs rapidly accumulate in the lung-draining mediastinal lymph nodes and lungs. BrdU incorporation studies indicate that Tregs undergo proliferation that contributes to their accumulation in the lymph nodes and lungs. Following an acute RSV infection, pulmonary Tregs modulate CD25 expression and acquire an activated phenotype characterized as CD11a(high), CD44(high), CD43(glyco+), ICOS(+), and CTLA-4(+). Surprisingly, in vivo depletion of Tregs prior to RSV infection results in delayed virus clearance concomitant with an early lag in the recruitment of RSV-specific CD8 T cells into the lungs. Additionally, Treg depletion results in exacerbated disease severity, including increased weight loss, morbidity, and enhanced airway restriction. In Treg-depleted mice there is an increase in the frequency of RSV-specific CD8 T cells that coproduce IFN-gamma and TNF-alpha, which may contribute to enhanced disease severity. These results indicate that pulmonary Tregs play a critical role in limiting immunopathology during an acute pulmonary virus infection by influencing the trafficking and effector function of virus-specific CD8 T cells in the lungs and draining lymph nodes.
Details
- Title: Subtitle
- Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection
- Creators
- Ross B Fulton - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USADavid K MeyerholzSteven M Varga
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.185(4), pp.2382-2392
- DOI
- 10.4049/jimmunol.1000423
- PMID
- 20639494
- PMCID
- PMC2923480
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI063520-04 / NIAID NIH HHS T32 AI007511 / NIAID NIH HHS R01 AI063520 / NIAID NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 08/15/2010
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology
- Record Identifier
- 9984083884102771
Metrics
21 Record Views