title: CD4+CD25+ regulatory T cells suppress the immune responses of mouse embryo fibroblasts to murine cytomegalovirus infection.
abstract: Cytomegaloviruses (CMVs) cause common viral infectious diseases and are difficult for the host immune system to eliminate, which leads to persistent or chronic infection. To investigate the T cell immune response stimulated by murine cytomegalovirus (MCMV) infection and the role of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) in this process, T cells containing various proportions of Tregs were co-cultured with MCMV-infected mouse embryo fibroblasts (MEFs). MCMV infection stimulated proliferation of effector T cells as well as differentiation to Tregs, which consequently increased the expression of TGF-beta and IL-10. The proliferation of Tc1 (CD3(+)CD8(+)IFN-gamma(+)), Th1 (CD3(+)CD4(+)IFN-gamma(+)), and Tc2 (CD3(+)CD8(+)IL-4(+)) subsets was significantly suppressed with an increased proportion of Tregs in the co-culture system. Treg-depleted T cells inhibited viral load when co-cultured with MCMV-infected MEFs, however, this inhibitory effect was diminished when an increased proportion of Tregs was introduced. The suppressing effects of Tregs on effector T cells were attenuated by the addition of monoclonal antibody to TGF-beta, but not the one to IL-10, suggesting that TGF-beta is a major messenger involved in the immune suppressing effect of Tregs.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Li
authors.forename: Xing-lou
authors.initials: XL
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yong-jian
authors.initials: YJ
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Fang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019562:Viral Load / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse