Methylprednisolone Inhibit Activated CD4~+ T Cell Survival Promoted By Toll-like Receptor Ligands

Objective:Methylprednisolone (MP) can affect the survival of CD4+ T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that Toll-Like Receptors (TLRs) on CD4+ T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4+ T cells. This study was designed to investigate the relationship between MP, TLRs and activated CD4+ T cells.Methods:We separated and purified CD4+ T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of NF-κB and AP-1. We then assessed CD4+ T cell survival and proliferation and the expression of NF-κB and AP-1.Results:Activated CD4+CD25-T cells showed increased TLR-3 and TLR-9 mRNA expression, but Polyinosinic:Polycytidylic Acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4+CD25-T cells, whereas MP reduced the survival of activated CD4+T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-κB inhibitor NBD inhibited the survival of activated CD4+CD25-T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-κB induced by poly I:C and CpG DNA in activated CD4+CD25-T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I: C and CpG DNA. Finally, the proliferation of activated CD4+CD25-T cells was not affected by poly I:C or MP. Conclusions:The survival of activated CD4+CD25-T cells is promoted by TLR ligands, but this effect is inhibited by MP.