Moore John W J, Beattie Lynette, Osman Mohamed, Owens Benjamin M J, Brown Najmeeyah, Dalton Jane E, Maroof Asher, Kaye Paul M
Centre for Immunology & Infection, Department of Biology and Hull York Medical School, University of York, York, United Kingdom.
PLoS One. 2016 Sep 22;11(9):e0163604. doi: 10.1371/journal.pone.0163604. eCollection 2016.
Recent thymic emigrants (RTEs) represent a source of antigen-naïve T cells that enter the periphery throughout life. However, whether RTEs contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. Here, we show that CD4+ recent thymic emigrants emerging into the periphery of mice with ongoing Leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. However, CD4+ RTEs displayed severely restricted differentiation either into IFNγ+ or IFNγ+TNFα+ effectors, or into IL-10-producing regulatory T cells. Effector cell differentiation in the chronically infected host was not promoted by adoptive transfer of activated dendritic cells or by allowing extended periods of post-thymic differentiation in the periphery. Nevertheless, CD4+ RTEs from infected mice retained the capacity to transfer protection into lymphopenic RAG2-/- mice. Taken together, our data indicate that RTEs emerging into a chronically inflamed environment are not recruited into the effector pool, but retain the capacity for subsequent differentiation into host protective T cells when placed in a disease-free environment.
近期胸腺迁出细胞（RTEs）是终生进入外周的初始T细胞来源。然而，RTEs是否有助于控制慢性寄生虫感染以及如何通过治疗干预来利用它们的潜力目前尚不清楚。在这里，我们表明，在利什曼原虫杜氏感染持续存在的小鼠外周出现的CD4⁺近期胸腺迁出细胞会经历部分激活，并被招募到肉芽肿性炎症部位。然而，CD4⁺RTEs向IFNγ⁺或IFNγ⁺TNFα⁺效应细胞或向产生IL-10的调节性T细胞的分化受到严重限制。在慢性感染宿主中，效应细胞的分化不会通过活化树突状细胞的过继转移或通过在外周允许延长的胸腺后分化时间来促进。尽管如此，来自感染小鼠的CD4⁺RTEs保留了将保护作用转移到淋巴细胞减少的RAG2⁻/⁻小鼠中的能力。综上所述，我们的数据表明，进入慢性炎症环境的RTEs不会被招募到效应细胞池中，但在置于无疾病环境时保留了随后分化为宿主保护性T细胞的能力。
