NF-kappa B-regulated suppression of T-bet in T cells represses Th1 immune responses in pregnancy

作者：McCracken Sharon A^*; Hadfield Katrina; Rahimi Zolaikha; Gallery Eileen D; Morris Jonathan M

来源：European Journal of Immunology, 2007, 37(5): 1386-1396.

DOI：10.1002/eji.200636322

• cytokines
• human
• T cells
• Th1/Th2 cells
• transcription factors

The molecular mechanisms that suppress Th1 immune responses in pregnancy are unknown. We assessed the expression of the Th1 cytokine transcription factor T-bet. We isolated PBMC and T cells from non-pregnant and pregnant women and demonstrated that T-bet is specifically down-regulated in pregnancy under basal and stimulated conditions. Low levels of T-bet protein were detected in the nuclear fraction of unstimulated PBMC from non-pregnant, but not pregnant women. Nuclear levels of T-bet increased in response to PMA/ionomycin in PBMC from non-pregnant, but not pregnant women. T-bet expression was greater in whole cell lysates of stimulated CD3(+) T cells from non-pregnant relative to pregnant women. NF-KB is specifically downregulated in T cells in pregnant women, resulting in suppressed expression of Th1 cytokines IL-2, IFN-gamma and TNF-cc. In this study, down-regulation of NF-KB also resulted in diminished expression of T-bet. PMA induces NF-KB translocation, T-bet expression and IL-2, IFN-gamma and TNF-a production. Conversely, pre-incubation with SN50, and NF-KB oligodeoxyribonucleotide decoys suppressed PMA-induced NF-KB translocation and gene transcription, respectively, resulting in diminished T-bet expression and Th1 cytokine production. Therefore, maintenance of the cytokine environment for pregnancy success is mediated via strict regulation of Th1 immune responses, more specifically through control of NF-KB and T-bet transcription.

• 出版日期2007-5
• 单位河北医科大学