日本一個(gè)研究團(tuán)隊(duì)報(bào)告說(shuō),，他們發(fā)現(xiàn)一種蛋白質(zhì)與調(diào)節(jié)細(xì)胞內(nèi)鈣濃度相關(guān),，是抑制性T細(xì)胞成熟所必需的,，如實(shí)現(xiàn)對(duì)這種蛋白質(zhì)分子的人工控制,，就有可能治療干燥綜合征,、多發(fā)性硬化癥等自體免疫疾病,。
健康人體免疫系統(tǒng)能區(qū)別自體與外來(lái)物質(zhì),，在攻擊入侵的細(xì)菌、病毒等病原體的同時(shí),，避免攻擊自身組織,。但是如果免疫反應(yīng)過(guò)度，免疫系統(tǒng)就會(huì)攻擊正常的細(xì)胞和組織,，導(dǎo)致過(guò)敏和自體免疫疾病等,。因此，何時(shí)激活或抑制免疫系統(tǒng)非常重要,。
在免疫系統(tǒng)中,，T細(xì)胞起著重要的作用,，這種淋巴細(xì)胞能識(shí)別病毒、細(xì)菌等異物并指揮其他免疫細(xì)胞進(jìn)攻異物,。而其中的抑制性T細(xì)胞亞群能對(duì)免疫系統(tǒng)起負(fù)向調(diào)節(jié)作用,。若其功能失常，則免疫反應(yīng)過(guò)強(qiáng),，會(huì)引發(fā)自體免疫疾病,。
東京醫(yī)科齒科大學(xué)副教授大洞將嗣的團(tuán)隊(duì)發(fā)現(xiàn)，基質(zhì)交感分子與抑制性T細(xì)胞的生成相關(guān),。他們培育出一批不能合成基質(zhì)交感分子1和基質(zhì)交感分子2的實(shí)驗(yàn)鼠,，發(fā)現(xiàn)這些實(shí)驗(yàn)鼠體內(nèi)完全不能產(chǎn)生抑制性T細(xì)胞。進(jìn)一步實(shí)驗(yàn)顯示,，在基質(zhì)交感分子的作用下,，鈣進(jìn)入細(xì)胞內(nèi)部，而鈣進(jìn)入細(xì)胞是抑制性T細(xì)胞增殖所必不可少的,。
研究人員在新一期《免疫》（Immunity）雜志網(wǎng)絡(luò)版上發(fā)表論文說(shuō),，基質(zhì)交感分子是人工培育和誘導(dǎo)抑制性T細(xì)胞的必需因子，實(shí)現(xiàn)對(duì)這種蛋白質(zhì)分子的人工控制,，就有可能治療多種自體免疫疾病,。（生物谷Bioon.com）
10.1016/j.immuni.2013.02.008
PMC:
PMID:
Agonist-Selected T Cell Development Requires Strong T Cell Receptor Signaling and Store-Operated Calcium Entry
Masatsugu Oh-horasend, Noriko Komatsu, Mojgan Pishyareh, Stefan Feske, Shohei Hori, Masaru Taniguchi, Anjana Rao
T cell receptor (TCR) signaling driven by interaction of the TCR with specific complexes of self-peptide and the major histocompatibility complex determines T cell fate in thymic development. However, the signaling pathway through which TCR signal strength regulates distinct T cell lineages remains unknown. Here we have used mice lacking the endoplasmic reticulum Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2 to show that STIM-induced store-operated Ca2+ entry is not essential for thymic development of conventional TCRαβ+ T cells but is specifically required for the development of agonist-selected T cells (regulatory T cells, invariant natural killer T cells, and TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes). The severe impairment of agonist-selected T cell development is mainly due to a defect in interleukin-2 (IL-2) or IL-15 signaling. Thus, STIM1 and STIM2-mediated store-operated Ca2+ influx, leading to efficient activation of NFAT (nuclear factor of activated T cells), is critical for the postselection maturation of agonist-selected T cells.
