2017年2月13日, 國際著名學術期刊《美國國家科學院院刊》雜誌線上發表了美國密蘇裡大學醫學院分子微生物學、免疫學與外科學Emma Teixeiro教授的一篇研究論文, 論文揭示了免疫系統內T細胞記憶病毒的機制, 對進一步瞭解免疫系統對抗病毒感染和回應有重要影響。 研究人員鑒定出在記憶T細胞中運行的一種分子機制, 這種機制可能在體內產生和維持更多的記憶T細胞。 這一發現有望能夠改進疫苗接種和癌症免疫療法。
當一種特定的病原菌首次攻擊身體時, 免疫系統中的t細胞協助抵抗它的感染。 在清除這種感染後,
Emma Teixeiro博士說:“疫苗和當前的一些基於T細胞的腫瘤療法依賴於產生記憶T細胞, 從而給病人提供完整和持久的結果。 我們發現利用分子或遺傳策略可能能夠增強在記憶T細胞中運行的一種重要的分子機制——NFkB-Pim1-Eomes軸, 從而有助於讓當前的疫苗或腫瘤療法更加有效。 針對特定的病原菌或癌症復發, 這可能有助降低疫苗再接種的次數。 ”
在之前的研究中,
“我們當前的研究強調了NFkB和Pim-1信號在維持T細胞記憶品質中發揮著意想不到的作用。 這些結果首次展示了在感染期間, NFkB信號如何調節記憶T細胞產生。 鑒定出兩種這樣的分子靶標可能有助設計更好的疫苗策略和腫瘤免疫療法。 ”Teixeiro說。
根據Teixeiro的說法,
原文連結:
NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-Cellmemory quality
原文摘要:
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expressionof high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness.
doi:10.1073/pnas.1608448114
作者:Emma Teixeiro 點擊:次