Study of the role of CD4+CD45RClowTreg in regulating immune tolerance of rats undergoing liver transplantation / 器官移植

ABSTRACT

Objective To investigate the role of CD4+CD45RClow regulatory T cell (Treg) in the immune tolerance induction of rats undergoing liver transplantation. Methods Liver transplantation rat models of acute rejection (AR) [Lewis→Brown Norway (BN), AR group] and spontaneous tolerance (BN→Lewis, tolerance group) were established, with 6 rats in each group. Moreover, 3 Lewis rats and 3 BN rats were assigned into the sham operation group (control group). The liver tissues of rats in each group were subject to pathological staining. The expression of T cell subsets and plasmacytoid dendritic cells (pDC) in the peripheral blood, liver graft and spleen of rats was detected in each group. The correlation between pDC and CD4+CD45RClowTreg was analyzed. The expression levels of CD4, CD45RC and CD103 in the liver graft and spleen of rats were quantitatively measured in each group. Results In the AR group, pathological manifestations mainly consisted of inflammatory cell infiltration and structure disorders of transplant liver. Compared with the AR group, the expression levels of CD4+CD25+Treg and CD8+Treg in the peripheral blood were significantly up-regulated in the tolerance group (all P < 0.05). In the peripheral blood, the expression level of CD4+CD25+Treg was positively correlated with that of CD8+Treg (r=0.742, P=0.022). In the AR group, the expression level of CD4+CD45RChighT cell in the peripheral blood was significantly higher than those in the tolerance and control groups (both P < 0.05). Compared with the AR group, the expression level of CD4+CD45RClowTreg in the spleen, and the expression levels of CD8+CD45RClowTreg in the peripheral blood, transplant liver and spleen were significantly up-regulated in the tolerance group (all P < 0.05). Compared with the control and AR groups, the ratio of CD8+CD45RClowTreg/CD8+T in the peripheral blood and the expression levels of pDC in the peripheral blood, transplant liver and spleen were all significantly up-regulated in the tolerance group (all P < 0.05). The expression level of CD4+CD45RClowTreg was positively correlated with the changes of pDC (r=0.506, P=0.016). The expression levels of CD4, CD45RC and CD103 in the transplant liver and spleen of rats were up-regulated in the tolerance group. In the AR group, the expression levels of CD4 and CD45RC were up-regulated, whereas that of CD103 was down-regulated. Conclusions CD4+CD45RClowTreg is a cell subgroup with negative immune regulation, which may construct a regulatory cell network of immune tolerance induction along with CD8+CD45RClowTreg and pDC.