title: IFN-γ- and IL-10-expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis.
abstract: Foxp3(+) CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein-specific Foxp3(+) T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3(+) T reg cells can be identified on the basis of cytokine production.
authors: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors: Jingxian
authors: J
authors: Zhao
authors: Jincun
authors: J
authors: Zhao
authors: Craig
authors: C
authors: Fett
authors: Kathryn
authors: K
authors: Trandem
authors: Erica
authors: E
authors: Fleming
authors: Stanley
authors: S
authors: Perlman
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001973:Bromodeoxyuridine; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma; D001973:Bromodeoxyuridine