[Synergistic immunomodulatory effects of interferon-gamma and bone marrow mesenchymal stem cells]

Chen Liang, Shu-lian Chen, Mei Wang, Wen-jing Zhai, Zheng Zhou, Ai-ming Pang, Si-zhou Feng, Ming-zhe Han
Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi 2013, 34 (3): 213-6

OBJECTIVE: To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs.

METHODS: ① MSCs were cultured in the presence or absence of IFN-γ(100 ng/ml), the supernatants were collected for measurements of PGE2、HGF and TGF-β1 by ELISA kits. ② MSCs were cultured in the presence or absence of IFN-γ (100 ng/ml)for 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenase(IDO)mRNA by semiquantitative RT-PCR. ③ Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit.

RESULTS: ①The immunosuppressive cytokines PGE2、HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/ml(P=0.011);(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/ml(P<0.001),respectively. ②The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. ③Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were (40.4±10.9)% vs(36.7±7.4)% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002].

CONCLUSION: ①Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. ②IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. ③MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.

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