據(jù)美國每日科學(xué)網(wǎng)站報道,，英國研究人員發(fā)現(xiàn)了一種可控制白血細(xì)胞老化的新機(jī)制，可扭轉(zhuǎn)免疫系統(tǒng)衰退,，提高老年人的免疫力,。該研究發(fā)表在《免疫學(xué)期刊》上。
隨著年齡的增長,，老年人免疫系統(tǒng)的效率開始下降,，因而容易感染重癥。這對他們的生活健康構(gòu)成了威脅,，也使其生活質(zhì)量明顯下降,。
由倫敦大學(xué)學(xué)院阿恩·阿克巴爾教授領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn)，人類免疫系統(tǒng)逐漸衰弱的原因是由于每次感染后會有一定比例的白血細(xì)胞失活,。雖然這種機(jī)制是進(jìn)化而來,，可以起到預(yù)防某些癌癥的作用，但隨著失活的白血細(xì)胞的比例不斷提高,，人體的防御系統(tǒng)也被削弱,。
研究表明，白血細(xì)胞失活是由一種尚不確定的免疫系統(tǒng)老化機(jī)制所導(dǎo)致,。此前科學(xué)家認(rèn)為,，免疫細(xì)胞老化與染色體端粒的長度有關(guān),。隨著白血細(xì)胞的不斷增殖，染色體端粒不斷縮短,，直至最后細(xì)胞永久失活,。這意味著，免疫細(xì)胞有一種內(nèi)置的壽命機(jī)制,。隨著人類壽命的延長,，免疫細(xì)胞將無法提供有效的保護(hù)。
阿克巴爾教授的研究小組在采集的血液樣本中發(fā)現(xiàn),，一些失活的白血細(xì)胞卻有著較長的端粒,，這表明白血細(xì)胞失活存在其他機(jī)制。而更令人興奮的是,，這些有著較長端粒的白血細(xì)胞不會處于永久失活狀態(tài),。
當(dāng)研究人員阻斷在實驗室中新確定的白血細(xì)胞的某個途徑時發(fā)現(xiàn)，白血細(xì)胞可以被重新激活,，而阻斷該途徑的藥物早已被開發(fā)出來,，用于治療其他疾病。所以研究人員下一步將研究重新激活老年人的白血細(xì)胞會帶來什么好處,。
研究人員表示,，雖然這種方法還不能讓人類永葆青春，但它可以提高老年人的免疫力,，幫助老年人戰(zhàn)勝各種感染性疾病,。此外，該研究還深化了人類對細(xì)胞生物學(xué)的認(rèn)識,，為控制人類的免疫系統(tǒng)開拓出全新的無法預(yù)見的未來,，對提高人類的生活質(zhì)量價值重大,。(生物谷 Bioon.com)
doi:10.4049/?jimmunol.1100978
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Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells
Diletta Di Mitri, Rita I. Azevedo, Sian M. Henson, Valentina Libri, Natalie E. Riddell, Richard Macaulay, David Kipling, Maria V. D. Soares, Luca Battistini and Arne N. Akbar
Persistent viral infections and inflammatory syndromes induce the accumulation of T cells with characteristics of terminal differentiation or senescence. However, the mechanism that regulates the end-stage differentiation of these cells is unclear. Human CD4+ effector memory (EM) T cells (CD27−CD45RA−) and also EM T cells that re-express CD45RA (CD27−CD45RA+; EMRA) have many characteristics of end-stage differentiation. These include the expression of surface KLRG1 and CD57, reduced replicative capacity, decreased survival, and high expression of nuclear γH2AX after TCR activation. A paradoxical observation was that although CD4+ EMRA T cells exhibit defective telomerase activity after activation, they have significantly longer telomeres than central memory (CM)-like (CD27+CD45RA−) and EM (CD27−CD45RA−) CD4+ T cells. This suggested that telomerase activity was actively inhibited in this population. Because proinflammatory cytokines such as TNF-α inhibited telomerase activity in T cells via a p38 MAPK pathway, we investigated the involvement of p38 signaling in CD4+ EMRA T cells. We found that the expression of both total and phosphorylated p38 was highest in the EM and EMRA compared with that of other CD4+ T cell subsets. Furthermore, the inhibition of p38 signaling, especially in CD4+ EMRA T cells, significantly enhanced their telomerase activity and survival after TCR activation. Thus, activation of the p38 MAPK pathway is directly involved in certain senescence characteristics of highly differentiated CD4+ T cells. In particular, CD4+ EMRA T cells have features of telomere-independent senescence that are regulated by active cell signaling pathways that are reversible.
