Human T cells modulate myeloid-derived suppressor cells through a TNF-α-mediated mechanism
Human T cells modulate myeloid-derived suppressor cells through a TNF-α-mediated mechanism
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DOI：
10.1016/j.imlet.2018.07.010
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Rieber, Nikolaus
中科院分区：
文献类型：
--
作者：
Bauswein, Markus;Singh, Anurag;Rieber, Nikolaus
骨髓源性抑制细胞（MDSC）代表一种先天免疫细胞亚群，能够抑制癌症和慢性炎症中的T细胞反应。虽然MDSC对T细胞的作用已经被彻底定义，但T细胞对MDSC稳态的相互影响仍然知之甚少。因此，我们全面分析了不同T细胞亚群对人MDSC产生和生存的影响。使用体外MDSC生成试验，我们证明了未刺激的CD 4（+）T细胞，而不是CD 8（+）T细胞，从CD 33（+）骨髓细胞诱导多形MDSC（PMN-MDSC）。这种作用依赖于直接的细胞-细胞接触，并需要TNF-α信号传导。可溶性TNF-α在PMN-MDSC的生成中是不稳定的，表明跨膜TNF-α参与了该跨细胞过程。刺激的人CD 3（+）T细胞延迟了PMN-MDSC的凋亡，这与TNF-α信号或直接细胞-细胞接触无关，但被IL-2重演。总之，我们的研究表明，人T细胞通过两种不同的机制调节MDSC的产生和存活，从而以受调节的方式微调人MDSC的稳态。
Myeloid-derived suppressor cells (MDSC) represent an innate immune cell subset capable of suppressing T-cell responses in cancer and chronic inflammation. While the effect of MDSC on T cells has been defined thoroughly, the reciprocal impact of T cells on MDSC homeostasis remains poorly understood. Therefore, we comprehensively analyzed the effect of different T-cell subsets on the generation and survival of human MDSC. Using an in vitro MDSC generation assay, we demonstrate that unstimulated CD4(+), but not CD8(+) T cells, induce polymorphonuclear MDSC (PMN-MDSC) from CD33(+) myeloid cells. This effect was dependent on direct cell-cell contact and required TNF-alpha signaling. Soluble TNF-alpha was dispensable for PMN-MDSC generation, suggesting that transmembrane TNF-alpha is involved in that trans-cellular process. Stimulated human CD3(+) T cells delayed the apoptosis of PMN-MDSC, which was independent of TNF-alpha signaling or direct cell-cell contact, but was recapitulated by IL-2. Taken together, our study shows that human T cells modulate MDSC generation and survival through two distinct mechanisms and thereby fine-tune the homeostasis of human MDSC in a regulated manner.