Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.
Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.
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DOI：
10.1084/jem.20142101
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发表时间：
2015-08-24
期刊：
影响因子：
--
通讯作者：
Scott P
中科院分区：
文献类型：
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作者：
Glennie ND;Yeramilli VA;Beiting DP;Volk SW;Weaver CT;Scott P
虽然感染利什曼原虫的人可能难以再感染，但人类疫苗尚未研制成功。Glennie等人鉴定出皮肤驻留的利什曼特异性记忆T细胞群体，这些细胞产生IFN-γ，并在随后的寄生虫感染中向皮肤招募循环T细胞。研究结果表明，一种成功的疫苗可能依赖于产生皮肤驻留记忆T细胞来产生有效的免疫反应。利什曼病在世界范围内造成重大疾病负担。虽然感染利什曼的患者在疾病消退后难以再感染，但人类疫苗尚未实现有效的免疫保护。虽然已知循环利什曼特异性T细胞在免疫中起关键作用，但外周组织中存在的记忆T细胞的作用尚未被探索。在这里，我们确定皮肤居民利什曼特异性记忆CD4+ T细胞群。这些细胞产生IFN-γ，并通过皮肤移植物移植到未成熟小鼠的皮肤上时仍留在皮肤中。它们的功能是以依赖于cxcr3的方式将循环T细胞募集到皮肤上，从而更好地控制寄生虫。我们的发现首次证明了CD4+ TRM细胞的形成是对寄生虫感染的反应，并表明对利什曼原虫的最佳保护性免疫，从而疫苗的成功，可能取决于循环和皮肤驻留记忆T细胞的产生。
While people infected with Leishmania can become refractory to reinfection, human vaccines have not yet been achieved. Glennie et al. identify a population of skin-resident Leishmania-specific memory T cells that produce IFN-γ and recruit circulating T cells to the skin in response to a subsequent parasitic infection. The findings indicate that a successful vaccine may be dependent on generating skin-resident memory T cells for an effective immune response. Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.