CD4+CD25+Treg Cells Prolong the Survival Time of Heart Allograft Via Induction Lymphocyte Apoptosis and Modulation the Ratio of T Cell Subsets
Author(s): Jinguo Zhu, Lihua Xiong
Background: CD4+CD25+regulatory T cells (CD4+CD25+ Treg cells) play major roles in immune regulation. Previous studies showed CD4+CD25+ Treg cells can maintain peripheral immune tolerance and increase the survival time of transplanted organs. However, the biological characteristics and the functional roles of these CD4+CD25+ Treg cells in transplantation tolerance remain unknown. The current study was conducted to observe the effect of CD4+CD25+ Treg cells on heart allograft in rats and to investigate the underlying mechanism of the CD4+CD25+ Treg cells.
Methods: 5 x 107 spleen cells of SD rats were inoculated into the thymus gland of Wistar rats. The level of CD4+CD25+ Treg cells was examined by the flow cytometry method, and the biological activity of CD4+CD25+ Treg cells was detected by the 3H-TdR method. Hearts were transplanted from SD rats (donors) to Wistar rats (recipients) and the animals were assigned into four groups: HT, HT+Ii,HT+Treg, HT+Treg+Ii. At various time points after the transplantation, the transplanted hearts were collected and histologically examined. The rate of lymphocyte apoptosis and T cell subsets in the peripheral blood of Wistar rats were analyzed with flow cytometry.
Results: The CD4+CD25+ Treg cells in Wistar rats were sharply increased, and these CD4+CD25+ Treg cells significantly extended the survival time: The mean survival time of the transplanted hearts was 8.1 ± 1.2 days, 35.7 ± 4.7 days, 53.7 ± 6.2 days, 75.7 ± 11.3 days in the group of HT, HT+Ii, HT+Treg, or HT+Ii+Treg, respectively (n = 12-14/group). Among them, the survival time between HT and HT+Treg or between HT and HT+Treg+Ii was significantly different (p<0.001). Also, we found that CD4+CD25+ Treg cells improved the pathological changes of the transplanted hearts, increased the rate of lymphocyte apoptosis, upregulated CD3+CD8+T cells, and suppressed CD3+CD4+ T cells.
Conclusions: CD4+CD25+ Treg cells appear to be able to induce tolerance in heart transplantation. This is largely due to the CD4+CD25+ Treg cells-dependent alteration of the ratio of T cell subsets and the induction of lymphocyte apoptosis.