Th17 cells are not required for maintenance of IL-17A-producing γδ T cells in vivo.
Th17 cells are not required for maintenance of IL-17A-producing γδ T cells in vivo.
复制标题
DOI：
10.1038/icb.2016.94
复制
发表时间：
2017-03
影响因子：
4
通讯作者：
Shilling RA
中科院分区：
文献类型：
--
作者：
Gupta PK;Wagner SR;Wu Q;Shilling RA
产生IL-17 A（γδT17）的γδ T细胞被认为在胸腺中自发发育，并在外周中维持。以前的研究表明，Th 17细胞通过表达TGFβ1在维持γδT17中发挥作用。然而，我们之前已经发现，在小鼠模型中，肺移植后γδT17细胞的扩增不需要Th 17细胞。使用CD 4 + T细胞中STAT 3缺陷的小鼠，其不能发育Th 17细胞，我们研究了在肺和淋巴组织中维持γδT17细胞对Th 17细胞和TGFβ1的需求。在稳态下，我们在这些小鼠的胸腺或外周中未发现γδT17细胞的缺陷。此外，在体外Th 17分化条件下，STAT 3缺陷型CD 4 + T细胞产生的TGFβ1水平显著高于野生型CD 4 + T细胞。为了确定STAT 3缺陷型CD 4 + T细胞是否可以在体内扩增γδT17细胞，我们使用了TCRβ−/−小鼠，已知它们在γδT17细胞中存在缺陷，可以被Th 17细胞拯救。然而，野生型Th 17细胞或大量CD 4 + T细胞的过继转移并不能扩增TCRβ−/−小鼠中的γδT17细胞。相反，IFN-γ+ γδ T细胞优先扩增，特别是在肺中。有趣的是，我们在体内和体外发现，TGFβ1可能负调节γδT17细胞库。我们的数据表明，Th 17细胞和TGFβ1不是γδT17细胞维持所必需的。
γδ T cells producing IL-17A (γδT17) are thought to develop spontaneously in the thymus and to be maintained in the periphery. Previous studies suggested a role for Th17 cells in the maintenance of γδT17 via the expression of TGFβ1. However, we have previously found that Th17 cells were not required for expansion of γδT17 cells after lung transplant in a mouse model. Using mice deficient in STAT3 in CD4+ T cells, which are unable to develop Th17 cells, we investigated the requirement for Th17 cells and TGFβ1 to maintain γδT17 cells in the lung and lymphoid tissues. At steady state, we found no defect in γδT17 cells in the thymus or periphery of these mice. Further, STAT3-deficient CD4+ T cells produced significantly higher levels of TGFβ1 than wild-type CD4+ T cells under Th17 differentiation conditions in vitro. To determine whether STAT3-deficient CD4+ T cells could expand γδT17 cells in vivo, we used TCRβ−/− mice, which are known to have a defect in γδT17 cells that can be rescued by Th17 cells. However, adoptive transfer of wild-type Th17 cells or bulk CD4+ T cells did not expand γδT17 cells in TCRβ−/− mice. In contrast, IFN-γ+ γδ T cells preferentially expanded, particularly in the lungs. Interestingly, we found in vivo and in vitro that TGFβ1 may negatively regulate the pool of γδT17 cells. Our data suggest that Th17 cells and TGFβ1 are not required for the maintenance of γδT17 cells.