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Methylprednisolone inhibits activated CD4+ T cell survival promoted by toll-like receptor ligands |
You-Sheng Lu, Li-Yong Pu, Xiang-Cheng Li and Xue-Hao Wang |
Nanjing, China
Author Affiliations: Liver Transplantation Center, First Affiliated Hospital (People s Hospital of Jiangsu Province), Nanjing Medical University, Nanjing 210029, China (Lu YS, Pu LY, Li XC and Wang XH)
Corresponding Author: Xue-Hao Wang, MD, PhD, Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China (Email: wang_xuehao@126.com) |
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Abstract BACKGROUND: 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.
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 nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). We then assessed CD4+ T cell survival and proliferation and the expression of NF-κB and AP-1.
RESULTS: 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-κB 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-κB 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.
CONCLUSION: The survival of activated CD4+ T cells is promoted by TLR ligands, but this effect is inhibited by MP.
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