Postthymic maturation influences the CD8 T cell response to antigen
Postthymic maturation influences the CD8 T cell response to antigen
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DOI：
10.1073/pnas.0812354106
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发表时间：
2009-03-24
影响因子：
11.1
通讯作者：
Fink, Pamela J.
中科院分区：
文献类型：
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作者：
Makaroff, Lydia E.;Hendricks, Deborah W.;Fink, Pamela J.
完整的T细胞发育需要胸腺后成熟，我们研究了这一本体论时期的CD8 T细胞对感染的反应的影响，通过比较成熟的CD8 T细胞与最近的胸腺移民（RTEs）的反应。当用非炎症刺激或细菌或病毒病原体激活时，与成熟的对应物相比，CD8 RTEs产生的产生精氨酸的效应细胞和长寿记忆前体的比例较低。尽管外周T细胞成熟在胸腺排出后几周内完成，但RTE衍生的记忆细胞继续表达不适当水平的记忆细胞标志物，并显示细胞因子产生的改变模式，甚至在感染后8周。当再激发时，RTE衍生的记忆细胞产生次级效应细胞，其在表型和功能上与其成熟对应物产生的效应细胞等同。在效应和记忆阶段的缺陷与T细胞受体，共刺激，或激活相关的细胞表面标志物的表达差异无关，但与较低的Ly6C表达水平在效应阶段。这项工作表明，胸腺后成熟的阶段影响细胞命运的决定和刺激的CD8 T细胞的细胞因子谱，在细胞从RTE隔室进展后很长时间内都有明显的影响。
Complete T cell development requires postthymic maturation, and we investigated the influence of this ontological period on the CD8 T cell response to infection by comparing responses of mature CD8 T cells with those of recent thymic emigrants (RTEs). When activated with a noninflammatory stimulus or a bacterial or viral pathogen, CD8 RTEs generated a lower proportion of cytokine-producing effector cells and long-lived memory precursors compared with their mature counterparts. Although peripheral T cell maturation is complete within several weeks after thymic egress, RTE-derived memory cells continued to express inappropriate levels of memory cell markers and display an altered pattern of cytokine production, even 8 weeks after infection. When rechallenged, RTE-derived memory cells generated secondary effector cells that were phenotypically and functionally equivalent to those generated by their mature counterparts. The defects at the effector and memory stages were not associated with differences in the expression of T cell receptor-, costimulation-, or activation-associated cell surface markers yet were associated with lower Ly6C expression levels at the effector stage. This work demonstrates that the stage of postthymic maturation influences cell fate decisions and cytokine profiles of stimulated CD8 T cells, with repercussions that are apparent long after cells have progressed from the RTE compartment.