Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche.
Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche.
复制标题
活性TGFβ细胞因子的竞争可以选择性地保留表皮生态裂市场中抗原特异性组织记忆T细胞。
DOI：
10.1016/j.immuni.2020.10.022
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发表时间：
2021-01-12
期刊：
影响因子：
32.4
通讯作者：
Kaplan DH
中科院分区：
文献类型：
--
作者：
Hirai T;Yang Y;Zenke Y;Li H;Chaudhri VK;De La Cruz Diaz JS;Zhou PY;Nguyen BA;Bartholin L;Workman CJ;Griggs DW;Vignali DAA;Singh H;Masopust D;Kaplan DH
在淋巴结中抗原驱动的扩增后，转化生长因子-β（TGFβ）是皮肤募集的CD 8 + T细胞效应器分化为表皮驻留记忆T细胞（Trm）及其表皮持久性所必需的。我们发现支持Trm细胞的TGFβ来源是自分泌的。此外，在皮肤中遇到同源抗原的抗原特异性Trm细胞和没有遇到同源抗原的旁观者Trm细胞在稳态条件下都显示出在表皮中的长期持久性。然而，当活性TGF β受到限制或当新的T细胞克隆被募集到表皮中时，抗原特异性Trm细胞比旁观者Trm细胞更有效地保留。在这两种情况下，基因增强的TGFβR信号传导允许旁观者Trm细胞与抗原特异性Trm细胞一样有效地持续存在于表皮中。因此，T细胞之间对活性TGFβ的竞争代表了一种未被重视的选择压力，其促进了抗原特异性Trm细胞在表皮小生境中的积累和持久性。CD 8+记忆T细胞的表皮驻留需要TGFβ，但这种细胞因子的来源和这种需求的相关性尚不清楚。Hirai等人揭示，自分泌TGFβ反式激活的克隆内竞争优先富集皮肤屏障处的抗原特异性T细胞。
Following antigen-driven expansion in lymph node, transforming growth factor-β (TGFβ) is required for differentiation of skin-recruited CD8+ T cell effectors into epidermal resident memory T cells (Trm) and their epidermal persistence. We found that the source of TGFβ supporting Trm cells was autocrine. In addition, antigen-specific Trm cells that encountered cognate antigen in the skin, and bystander Trm cells that did not, both displayed long-term persistence in the epidermis under steady-state conditions. However, when the active-TGFβ was limited or when new T cell clones were recruited into the epidermis, antigen-specific Trm cells were more efficiently retained than bystander Trm cells. Genetically enforced TGFβR signaling allowed bystander Trm cells to persist in the epidermis as efficiently as antigen-specific Trm cells in both contexts. Thus, competition between T cells for active TGFβ represents an unappreciated selective pressure that promotes the accumulation and persistence of antigen-specific Trm cells in the epidermal niche. Epidermal residence of CD8+ memory T cells requires TGFβ, but the source of this cytokine and the relevance of this requirement are unclear. Hirai et al. reveal that intraclonal competition for transactivation of autocrine TGFβ preferentially enriches for antigen-specific T cells at the skin barrier.
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