Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection.
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.
Immunology Program, Benaroya Research Institute, Seattle, WA 98101.
Shivani
S
Srivastava
Meghan A
MA
Koch
Marion
M
Pepper
Daniel J
DJ
Campbell
D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism* / Q000494:pharmacology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*
D017931:DNA Primers; D007370:Interferon Type I