LF 15-0195 Generates Synergistic Tolerance by Promoting Formation of CD4+CD25+CTLA4+ T Cells

Abstract

The purpose of the present study was to investigate the influence of 15-deoxyspergualin (LF) on the phenotypes and functions of dendritic cells (DCs) and T cells and to further illustrate the mechanism of LF-inducing immunologic tolerance. DCs from mice were cultured and treated with varying doses of LF at specific time-points. Fluorescence-activated cell sorting (FACS) was used to verify the changes of phenotypes in the cultured DCs labeled with fluorescent antibody. DCs were also used as stimulators in mixed leukocyte reaction to detect their ability to stimulate T-cell proliferation. DCs and T cells, treated with or without LF, were cultured together; phenotypes and cytokine profile of the T cells were identified and assayed by FACS and enzyme-linked immunosorbent assay. LF induced a dose- and time-dependent suppression of maturation of DCs and a dose-dependent suppression of T-cell proliferation in mixed leukocyte reaction when LF-treated DCs were used as stimulators. LF-treated DCs, cultured with naive T cells, could promote the formation of CD4+CD25+CTLA4+ T-cell subtypes and the production of higher levels of interleukin-10. It was suggested that the mechanism of LF-induced tolerance was inhibiting maturation and function of DC and inducing the formation of regulatory T-cell subtype by "suppressor DCs" to achieve a new immune balance.