IFN-?– and IL-10–expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis

Zhao, Jingxian; Zhao, Jincun; Fett, Craig; Trandem, Kathryn; Fleming, Erica; Perlman, Stanley

Regulatory CD4 T cells (T reg cells), which are characterized by expression of Foxp3, are major contributors to the antiinflammatory response in the settings of autoimmune disease, cancer, and infections (Vignali et al., 2008) . In infectious settings, they help to resolve the proinflammatory response, thereby minimizing bystander damage but also potentially delaying or preventing pathogen clearance (Belkaid, 2007) . T reg cells may also be required for efficient immune cell entry into sites of infection (Lund et al., 2008) . Pathogen-specific T reg cells have been detected in a few studies using whole pathogen preparations as targets, without identification of specific target epitopes. In mice infected with Leishmania major or Toxoplasma gondii, parasitespecific T reg cells were demonstrated, but the target antigen or epitope was not further identified (Suffia et al., 2006; Oldenhove et al., 2009) . In another study, T reg cells specific for a Mycobacteria tuberculosis epitope (Mtb) were studied using Mtb-specific TCR Tg cells, but T reg cells specific for this epitope were not found in the natural infection and no Mtb-specific T reg cell target epitope has thus far been identified (Shafiani et al., 2010) . Identification of pathogen-specific epitopes recognized by T reg cells would facilitate their study and therapeutic use in disease settings.