CD4+CD25+ regulatory T cells suppress the immune responses of mouse embryo fibroblasts to murine cytomegalovirus infection.
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.
Li
Ya-nan
YN
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Liu
Xing-lou
XL
Huang
Fei
F
Zhou
Hua
H
Huang
Yong-jian
YJ
Fang
Feng
F
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
D019138:Antibodies, Blocking; D015703:Antigens, CD; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse