CD4+CD25+Treg Cells Prolong the Survival Time of Heart Allograft Via Induction Lymphocyte Apoptosis and Modulation the Ratio of T Cell Subsets

Abstract

Background: CD4CD25regulatory T cells (CD4CD25 Treg cells) play major roles in immune regulation. Previous studies showed CD4CD25 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 CD4CD25 Treg cells in transplantation tolerance remain unknown. The current study was conducted to observe the effect of CD4CD25 Treg cells on heart allograft in rats and to investigate the underlying mechanism of the CD4CD25 Treg cells. Methods: 5 x 10 spleen cells of SD rats were inoculated into the thymus gland of Wistar rats. The level of CD4CD25 Treg cells was examined by the flow cytometry method, and the biological activity of CD4CD25 Treg cells was detected by the H-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 Cardiol Cardiovasc Med 2022; 6 (2): 71-82 DOI: 10.26502/fccm.92920245 Cardiology and Cardiovascular Medicine Vol. 6 No. 2 – April 2022. [ISSN 2572-9292] 72 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 CD4CD25 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 CD4CD25 Treg cells improved the pathological changes of the transplanted hearts, increased the rate of lymphocyte apoptosis, upregulated CD3CD8T cells, and suppressed CD3CD4 T cells. Conclusions: CD4CD25 Treg cells appear to be able to induce tolerance in heart transplantation. This is largely due to the CD4CD25 Treg cellsdependent alteration of the ratio of T cell subsets and the induction of lymphocyte apoptosis.