Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 211, Issue 5, Pages 961-974Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20131556
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Funding
- National Cancer Institute training grant from the Department of Immunology at the University of Washington School of Medicine
- [AR055695]
- [AI067750]
- [AI085130]
- [HL098067]
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Regulatory T (T reg) cells play an essential role in preventing autoimmunity but can also impair clearance of foreign pathogens. Paradoxically, signals known to promote T reg cell function are abundant during infection and could inappropriately enhance T reg cell activity. How T reg cell function is restrained during infection to allow the generation of effective antiviral responses remains largely unclear. We demonstrate that the potent antiviral type I interferons (IFNs) directly inhibit co-stimulation-dependent T reg cell activation and proliferation, both in vitro and in vivo during acute infection with lymphocytic choriomeningitis virus (LCMV). Loss of the type I IFN receptor specifically in T reg cells results in functional impairment of virus-specific CD8(+) and CD4(+) T cells and inefficient viral clearance. Together, these data demonstrate that inhibition of T reg cells by IFNs is necessary for the generation of optimal antiviral T cell responses during acute LCMV infection.
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