Influence of high mobility group box-1 protein on the correlation between regulatory T cells and CD4+ CD25- T cells of spleen in mice.
- Author:
Ying ZHANG
1
;
Yong-Ming YAO
;
Yan YU
;
Yao WU
;
Zhi-Yong SHENG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Communication; drug effects; Cells, Cultured; HMGB1 Protein; pharmacology; Interleukin-10; metabolism; Interleukin-2; metabolism; Male; Mice; Mice, Inbred BALB C; Receptors, Interleukin-2; Spleen; cytology; T-Lymphocytes, Regulatory; drug effects; immunology; metabolism
- From: Chinese Journal of Surgery 2008;46(3):217-220
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the influence of high mobility group box-1 protein (HMGB1) on the immunosuppression function of splenic regulatory T cells (Tregs) and its potential regulatory mechanism underlying the effect on CD4+ CD25- T cells in mice.
METHODSCD4+ CD25+ Tregs isolated from the spleens of male BALB/c mice by magnetic beads were seeded on 96-well (1 x 10(5) cells/well) cell culture plates coated with 1 microg/ml anti-CD3 and soluble CD28. After being stimulated with HMGB1 for different time and concentrations, the secretions of IL-2 and IL-10 were analyzed by ELISA. Tregs stimulated for 72 hours were cultured with CD4+ CD25- T cells together. The suppressive activity of CD4+ CD25+ Treg to CD4+ CD25- T cells was analyzed by MTT test. IL-2, IL-10, IL-4, and interferon (IFN)-gamma in the cell suspensions were determined by ELISA.
RESULTSAfter stimulation with HMGB1, the suppressive activity of splenic Tregs in mice were significantly down-regulated at 72 hours, when the proportion of Tregs to CD4+ CD25- T cells was 1 : 1. The secretion of IL-2 of Tregs stimulated by HMGB1 was not markedly changed (P > 0.05), while a dose-dependent decrease between IL-10 induction and HMGB1 concentration was obviously (P < 0.05). When CD4+ CD25- T cells were cultured with stimulated Tregs, comparing with unstimulated-Treg group, levels of IL-2 and IFN-gamma were elevated following the increased concentration of HMGB1 (P < 0.05 or P < 0.01). Meanwhile the secretion of IL-4 and IL-10 significantly decreased when cultured with stimulated Tregs (P < 0.05).
CONCLUSIONSThese data suggested that HMGB1 stimulation can result in significant down-regulation of immunosuppression of splenic Tregs in mice. HMGB1 might be a potential immunoregulatory signal that influences the proliferation of effector T cells, secretion of IL-2 and cells-polarization by inhibiting CD4+ CD25+ Tregs activity.