Abstract

BACKGROUND: CD8+ cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4+CD25+ regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4+CD25+ Treg cells on CD8+ CTL depends on EXOs remains unknown and needs to be explored.

MATERIAL AND METHODS: We purified CD4+CD25+ Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4+CD25+ Treg cells and CD4+CD25+ Treg cells-derived EXOs on CD8+ CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated.

RESULTS: We successfully obtained EXOs from CD4+CD25+ Treg cells. The inhibition effect of EXOs on CD8+ CTL was concentration-dependent. In addition, the inhibition effect of CD4+CD25+ Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4+CD25+ Treg cells-released EXOs can prolong liver allograft survival.

CONCLUSIONS: CD4+CD25+ Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.

Keywords: Allografts, CD8-Positive T-Lymphocytes, exosomes, CD4 Antigens, Liver, Liver Transplantation, Mice, Inbred BALB C, Rats, Wistar, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Regulatory, Transplantation Tolerance