title: Effect of Regulatory T Cells on Promoting Apoptosis of T Lymphocyte and Its Regulatory Mechanism in Sepsis.
abstract: With both in vivo and in vitro experiments, the present study was conducted to investigate the effect of regulatory T cell (Treg) on promoting T-lymphocyte apoptosis and its regulatory mechanism through transforming growth factor-beta (TGF-β1) signaling in mice. A murine model of polymicrobial sepsis was reproduced by cecal ligation and puncture (CLP); PC61 and anti-TGF-β antibodies were used to decrease counts of CD4(+)CD25(+) Tregs and inhibit TGF-β activity, respectively. Splenic CD4(+)CD25(+) Tregs and CD4(+)CD25(-) T cells were isolated. Phenotypes, including cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), forkhead/winged helix transcription factor p3 (Foxp3), and TGFβ1(m+), as well as the apoptotic rate of CD4(+)CD25(-) T cell, were analyzed by flow cytometry. Real-time reverse transcription-polymerase chain reaction was performed to determine mRNA expression of TGF-β1, and the expressions of Smad2/Smad3, Bcl-2 superfamily members of Bcl-2/Bim, cytochrome C, the mitochondrial membrane potential, and caspases in CD4(+)CD25(-) T cells were simultaneously determined. After treatment with PC61 or anti-TGF-β antibody, CTLA-4, Foxp3, and TGFβ1(m+) expressions of CD4(+)CD25(+) Tregs were markedly decreased in comparison to that of the CLP group and the apoptosis rate of CD4(+)CD25(-) T cells was significantly positively correlated with the expression of TGF-β1. Meanwhile, levels of P-Smad2/P-Smad3, proapoptotic protein Bim, cytochrome C, and activity of caspase-3, -8, -9 were downregulated, whereas the mitochondrial membrane potential and antiapoptotic protein Bcl-2 expression were restored. Taken together, our data indicated that the TGF-β1 signal could be partly involved in the apoptosis of CD4(+)CD25(-) T cells promoted by CD4(+)CD25(+) Tregs, therefore inhibition of TGF-β1 expression may provide a novel strategy for the improvement of host immunosuppression following sepsis.
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Ying-yi
authors: YY
authors: Luan
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Cheng-fen
authors: CF
authors: Yin
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Qing-hua
authors: QH
authors: Qin
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Ning
authors: N
authors: Dong
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Xiao-mei
authors: XM
authors: Zhu
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Zhi-yong
authors: ZY
authors: Sheng
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Qing-hong
authors: QH
authors: Zhang
authors: Department of Microbiology and Immunology, Trauma Research Center , First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China .
authors: Yong-ming
authors: YM
authors: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D060908:CTLA-4 Antigen / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D056747:Immunomodulation; D016130:Immunophenotyping; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D045304:Cytochromes c; D020169:Caspases