Detection of monocyte-derived costimulatory molecule expression and the role during discordant xenogeneic immune responses
- VernacularTitle:人单核细胞共刺激分子在异种免疫反应中的表达及其作用机制
- Author:
Yusong FANG
;
Zidong LIU
;
Liangming ZHU
;
Pu WANG
;
Yunshan WANG
;
He XU
- Publication Type:Journal Article
- Keywords:
Monocytes;
CD4-positive T-lymphocytes;
Endothelial cells;
Transplantation,heterologous
- From:
Chinese Journal of Organ Transplantation
2008;29(10):589-593
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the expression and the role of monocyte-derived costimulatory molecuels during xenogeneic immune responses. Methods Porcine endothelial cells (PEC) were isolated from aorta, and subcultures were performed. CD4+ cells and monocytes were purified from human peripheral blood mononuclear cells (PBMC). PBMC-PEC co-cultures were established, and the cells were collected followed by staining with florescent-labeled monoclonal antibodies and analyzing by FACS. In selected experiments, monoclonal antibodies specific for CD154, CD80 and CD86 were added into PBMC-PEC co-cultures, and the effects of co-stimulatory molecule blockade in inhibiting lymphocyte proliferation in response to PEC were determined by 3H-thymidine up-take. The proliferation of CD4+ cells induced by PEC-conditioned monocytes with or without co-stimulation blockade was evaluated. Results PBMC-PEC co-incubation demonstrated dramatic lymphocyte proliferation as determined by 3H-thymidine up-take. FACS found that resting monocytes expressed only CD86 but not CD40 and CD80. CD14+ monocytes from PEC-stimulated PBMC demonstrated up-regulation of CD80 and CD40 expression. The up-regulation of CD86 was revealed. PEC-activated monocytes induced CD4+ cell proliferation while resting monocytes did not and this proliferation was inhibited by anti-CD154, anti-CD80 or anti-CD86 antibodies. Conclusions CD14+ monocytes play an important role during xenogeneie immune responses in indirect antigen presentation and co-stimulation- The interaction between monocyte-derived co-stimulatory molecules and CD4+ cell-derived CD154 and CD28 delivers secondary signal and induces CD4+ proliferation, and the co-stimulation blockade inhibits xe-nogeneic cell-mediated immune responses.