近日,，Journal of Clinical Investigation雜志發(fā)表的一項(xiàng)研究結(jié)果證實(shí)，一種重要的免疫細(xì)胞可以在人類扁桃體中生成,。這類細(xì)胞被稱為T淋巴細(xì)胞或T細(xì)胞,。此前，T細(xì)胞被認(rèn)為只在胸腺中產(chǎn)生。
這項(xiàng)由俄亥俄州立大學(xué)綜合癌癥中心的研究人員開展的研究可能將提升沃恩對(duì)T細(xì)胞癌癥以及自免疫疾病的理解,，以及加深對(duì)干細(xì)胞移植的認(rèn)識(shí),。
這項(xiàng)研究在人類扁桃體中確認(rèn)了5個(gè)截然不同發(fā)育階段的T細(xì)胞。這些階段與在胸腺中的T細(xì)胞發(fā)育階段十分相似,，不過研究人員也發(fā)現(xiàn)存在一些差異,。
該研究還發(fā)現(xiàn),，這些T細(xì)胞是在靠近扁桃體的纖維支架的特定區(qū)域發(fā)育的,。“我們很早就知道，一個(gè)功能完好的胸腺是產(chǎn)生完整功能T細(xì)胞所不可缺少的,，但是T細(xì)胞工廠是否存在于胸腺以外的地方一直都有爭議,，”研究的作者、俄亥俄州立大學(xué)綜合癌癥中心的Michael A. Caligiuri博士說,。
“我相信,，我們的研究將回答這個(gè)問題。這是首次對(duì)T細(xì)胞在胸腺外的全面,、逐步發(fā)育進(jìn)行報(bào)道,。”
該發(fā)現(xiàn)同時(shí)也引發(fā)了許多問題，Caligiuri提醒道,，目前仍然不清楚在扁桃體中產(chǎn)生的這些T細(xì)胞是否也在扁桃體中發(fā)育成熟,，或者它們是否離開扁桃體去別的地方發(fā)育成熟。
“這個(gè)現(xiàn)象對(duì)人類健康及疾病的全部啟示意義目前還不完全清楚,，”研究的第一作者Susan McClory說,。“這可能對(duì)T細(xì)胞癌癥及自免疫疾病的發(fā)生非常重要，或者也表明當(dāng)胸腺功能衰弱后扁桃體成為T細(xì)胞產(chǎn)生的另一個(gè)地方,。我們希望進(jìn)行進(jìn)一步的研究來發(fā)現(xiàn)這些可能性,。”她說。
研究人員利用從常規(guī)小孩扁桃體切除手術(shù)中獲取扁桃體組織并開展實(shí)驗(yàn),。依據(jù)T細(xì)胞在胸腺中發(fā)育的分子特征,，研究人員在扁桃體組織中確認(rèn)了5種成熟期中的T細(xì)胞。他們發(fā)現(xiàn),，其中兩組細(xì)胞與胸腺中產(chǎn)生的最早期T細(xì)胞類似,，而第5組細(xì)胞與胸腺中接近成熟的T細(xì)胞類似。
研究人員還發(fā)現(xiàn),，所有這5種細(xì)胞都可以在實(shí)驗(yàn)室條件下發(fā)育為T細(xì)胞,，其中四種還可以發(fā)育成為被稱為自然殺傷細(xì)胞的免疫細(xì)胞。
“總的來說,，我們的工作顯示扁桃體也可以與胸腺一樣作為T細(xì)胞工廠,，”Caligiuri說。“接下來我們需要弄明白來自扁桃體的T細(xì)胞的比例是多少。”（生物谷Bioon.com）
doi:10.1172/JCI46125
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Evidence for a stepwise program of extrathymic T cell development within the human tonsil
Susan McClory, Tiffany Hughes, Aharon G. Freud, Edward L. Briercheck, Chelsea Martin, Anthony J. Trimboli, Jianhua Yu, Xiaoli Zhang, Gustavo Leone, Gerard Nuovo andMichael A. Caligiuri
The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin– cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34+CD38brightLin– cells; (c) CD34+CD1a+CD11c– cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34–CD1a+CD3–CD11c– cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e) CD34–CD1a+CD3+CD11c– cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre–T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development.
