CD4+ T-Cell Converted Double Negative T-Cells Suppress B-Cells Proliferation and IGG Production in Mice.

Abstract

We have reported that CD4+ T-cells could be converted to CD3+CD4-CD8-(DN) T-cells, the converted DN T-cells were very potent in suppressing antigen-specific T cells responses in vitro and prolonged islet allograft survival in vivo. In this study, we further tested the functional potential of CD4+ T-cells converted DN T-cells on B-cells. We found that the proliferation of B-cells were significantly suppressed by DN T-cells and IgG secretion of stimulated B cells was also inhibited by DN T-cells in vitro and in vivo. The suppression was cell dose dependent and was relied on cell-cell contact. Perforin, a cytotoxic lymphocyte related cytokine, was highly expressed by DN T-cells, played an important role in DN T-cell mediated suppression, the potency of DN T-cells derived from perforin KO mice to suppress the proliferation of B-cells was significantly lower than that from wild type mice. Our study suggested that ex vivo CD4+ T-cells converted DN T-cells have the potential to down-regulate immune responses by suppressing B cells proliferation and IgG production. It supports the concept and the feasibility of potentially utilizing this novel cell-based therapeutic approach clinically for the prevention and treatment of B-cell mediated rejection.