title: The potential effect and mechanism of high-mobility group box 1 protein on regulatory T cell-mediated immunosuppression.
abstract: To investigate the effect of high-mobility group box 1 (HMGB1) protein on the regulatory T cells (Tregs) in vitro and its potential regulating mechanism in mice. Splenic CD4(+)CD25(+) Tregs and CD4(+)CD25(-) T cells were isolated. The time-dependent and dose-dependent responses between HMGB1 stimulation and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and forkhead/winged helix transcription factor p3 (Foxp3) expressions were analyzed. The secretion of various cytokines in the cell suspensions and the proliferation of CD4(+)CD25(-) T cells were determined. HMGB1 was found to be able to markedly down-regulate the expressions of CTLA-4 and Foxp3, especially at 72 h group and in 1,000 ng/mL group (both P < 0.01). The expression of Foxp3 mRNA showed a similar tendency as Foxp3 protein (P < 0.05 or P < 0.01). The secretion of interleukin (IL)-10 from Tregs was decreased when the concentration of HMGB1 was increased. The suppressive activity of proliferation of CD4(+)CD25(-) T cells exceeded 90% when the ratio of Tregs to CD4(+)CD25(-) T cells was 1:1; meanwhile, the proliferation of CD4(+)CD25(-) T cells was enhanced when cultured with HMGB1-stimulated Tregs. In the culture of HMGB1-stimulated Tregs, IL-2 and interferon-γ levels were elevated; whereas IL-4 and IL-10 decreased in CD4(+)CD25(-) T cells after the increased concentration of HMGB1 in comparison with unstimulated-Treg group. HMGB1 stimulation can result in markedly down-regulatory expressions of CTLA-4 as well as in Foxp3 expression and secretion of IL-10 from splenic Tregs in mice. HMGB1 appears to be involved in modulating cell-mediated immunity by influencing proliferation of effector T cells, secretion of IL-2, and cell polarization.
authors.affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Li-feng
authors.initials: LF
authors.lastname: Huang
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D024243:HMGB1 Protein / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D024243:HMGB1 Protein