Methylprednisolone inhibits activated CD4+ T cell survival promoted by toll-like receptor ligands
Lu, Y.-S.; Pu, L.-Y.; Li, X.-C.; Wang, X.-H.
Hepatobiliary and Pancreatic Diseases International Hbpd Int 9(4): 376-383
2010
ISSN/ISBN: 1499-3872 PMID: 20688601 Document Number: 641642
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 aimed to investigate the relationship between MP, TLRs and activated CD4+ T cells. We separated and purified CD4+ T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1). We then assessed CD4+ T cell survival and proliferation and the expression of NF-kappaB and AP-1. Activated CD4+ 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+ 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-kappaB essential modifier-binding domain (NBD) inhibited the survival of activated CD4+ 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-kappaB induced by poly I:C and CpG DNA in activated CD4+ 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+ T cells was not affected by poly I:C or MP. The survival of activated CD4+ T cells is promoted by TLR ligands, but this effect is inhibited by MP.