Skin Resident Memory CD4+ T Cells Enhance Protection Against Leishmania Major Infection

Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection following disease resolution, effective immune protection has not yet been achieved by human vaccines. While 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 IFNγ, and remain resident in the skin when transplanted by skin graft onto naïve 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. Two conditions were analyzed. For each condition, four mice were used, resulting in eight samples in total.

利什曼病(Leishmaniasis)在全球范围内造成了显著的疾病负担。尽管利什曼原虫(Leishmania)感染患者在疾病痊愈后可对再感染产生抵抗力，但目前人类疫苗仍未实现有效的免疫保护。已知循环利什曼原虫特异性T细胞在免疫应答中发挥关键作用，但外周组织中记忆T细胞的功能尚未得到探索。
本研究鉴定出一类皮肤驻留型利什曼原虫特异性记忆性CD4+ T细胞。这类细胞可分泌干扰素γ(IFNγ)，当通过皮肤移植移植至未致敏小鼠体内时，仍可驻留于皮肤组织中。它们能够以依赖趋化因子受体CXCR3(CXCR3)的方式招募循环T细胞至皮肤，从而更有效地控制寄生虫。
本研究的发现首次证实，CD4+组织驻留记忆T细胞(CD4+ TRM cells)可在寄生虫感染过程中形成，并提示针对利什曼病的最优保护性免疫（进而实现疫苗研发的成功）可能依赖于同时诱导循环记忆T细胞与皮肤驻留记忆T细胞的产生。
本研究共分析两组实验条件，每组使用4只小鼠，总计获得8份样本。