最近,，研究人員在人身體與環(huán)境打交道的部分(如皮膚,、肺部和胃腸道)發(fā)現一類非常重要的被稱作記憶T細胞(memory T cell)的免疫細胞,。然而,，這些“常駐” 記憶T細胞如何產生仍是一個謎,。為了揭示它們在我們的免疫系統(tǒng)如何記住病原體初次感染和如何阻止再次感染中發(fā)揮的重大作用,，研究人員一直在廣泛地開展研究,。
如今,，美國布萊根婦女醫(yī)院(Brigham and Women's Hospital) 皮膚科主任和哈佛大學皮膚醫(yī)學教授Thomas S. Kupper博士與研究員Xiaodong Jiang博士領導的一個研究小組使用一種涉及牛痘病毒感染皮膚的模型來解答關于這些新發(fā)現的細胞如何保護我們免受再次感染的重要問題。2012年2月29日,，相關研究結果發(fā)表在《自然》期刊上,。
Jiang和Kupper利用牛痘病毒感染皮膚來研究中央型記憶T細胞(central memory T cell，即在血液循環(huán)流通的T細胞)和常駐型記憶T細胞(resident memory T cell)在保護性免疫中所起的相對作用,。他們發(fā)現在牛痘病毒感染之后,，疾病特異性T細胞不僅是被快速地招募至感染位點，而且也被招募至皮膚所有區(qū)域,。
他們進一步證實隨后又遭遇的多次牛痘病毒感染導致在皮膚上積累起更加多的常駐型記憶T細胞,，而且這些細胞在皮膚內能夠長時間保持存在。
最后,，Jiang和Kupper第一次證實常駐型記憶T細胞在對抗感染上是最重要的保護性免疫細胞,，比中央型記憶T細胞還要重要，因為中央型記憶T細胞本身產生的快速免疫保護效率不高,。
“發(fā)現在保護性免疫中常駐型記憶T細胞比中央型記憶T細胞更加重要是令人吃驚的,，這使得我們不得不重新思考當前的免疫法則(immunologic dogma)”， Kupper說,。
盡管這項研究使用皮膚作為模式系統(tǒng),，但是這些結果能夠外推至肺部、胃腸道和其他與外部環(huán)境打交道的其他上皮組織,。
這些發(fā)現揭示著對傳染病產生記憶的起著重要作用的T細胞可能常駐于組織中,，而不是血液里,。
“免疫系統(tǒng)在合適場所和時間提供合適的T細胞來保護我們不受充滿著潛在有害性病原體的環(huán)境的影響”， Kupper說,。
這些發(fā)現也提示著人們應當對疫苗進行優(yōu)化以便準確地產生這類在組織中長期持續(xù)存在的常駐型記憶T細胞,，同時也提示著人們當前在開發(fā)疫苗時集中注意力于抗體生產可能并不是如此重要。
“這項研究提示著人們應當對如何構建和遞送疫苗進行根本性的重新評估”,， Kupper說,，“這些結果改變著我們考慮免疫系統(tǒng)和接種抗傳染病疫苗的方式。” (生物谷：towersimper編譯)
doi:10.1038/nature10851
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Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
Xiaodong Jiang, Rachael A. Clark, Luzheng Liu, Amy J. Wagers, Robert C. Fuhlbrigge & Thomas S. Kupper
Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (TRM) cells has been proposed. Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8+ skin TRM cells that reside within the entire skin. These skin TRM cells are potent effector cells, and are superior to circulating central memory T (TCM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8+ T cells are rapidly recruited to skin after acute VACV infection. CD8+ T-cell recruitment to skin is independent of CD4+ T cells and interferon-γ, but requires the expression of E- and P-selectin ligands by CD8+ T cells. Using parabiotic mice, we further show that circulating CD8+ TCM and CD8+ skin TRM cells are both generated after skin infection; however, CD8+ TCM cells recirculate between blood and lymph nodes whereas TRM cells remain in the skin. Cutaneous CD8+ TRM cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8+ skin TRM cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating TCM but no skin TRM cells showed greatly impaired viral clearance, indicating that TRM cells provide superior protection. Finally, we show that TRM cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective TRM cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.
