CD8⁺ T cells not only are critical mediators of adaptive immunity but also may exhibit innate-like properties such as surface expression of NKG2C, an activating receptor typically associated with natural killer (NK) cells. We demonstrate that, similar to NK cells, NKG2C⁺TCRαβ⁺CD8⁺ T cells are associated with prior human cytomegalovirus (HCMV) exposure. In addition to expressing several NK cell markers such as CD56 and KIR, NKG2C⁺CD8⁺ T cells are oligoclonal and do not up-regulate PD-1 even in response to persistent activation. Furthermore, we found that NKG2C⁺CD8⁺ T cells from some individuals exhibited strong effector function against leukemia cells and HCMV-infected fibroblasts, which was dictated by both NKG2C and TCR specificity. Transcriptomic analysis revealed that the transcription factor BCL11B, a regulator of T cell developmental fate, is down-regulated in NKG2C⁺CD8⁺ T cells when compared with conventional NKG2C⁻CD8⁺ T cells. BCL11B deletion in conventional CD8⁺ T cells resulted in the emergence of a similar innate-like CD56⁺CD94⁺DAP12⁺NKG2C⁺CD45RA⁺CCR7⁻PD-1^−/low T cell population with activity against HLA-E⁺ targets. On the basis of their intrinsic capacity to recognize diseased cells coupled with lack of PD-1 induction, NKG2C⁺CD8⁺ T cells represent a lymphocyte population that resides at the boundary between innate and adaptive immunity, presenting an attractive alternative for cellular therapy, including CAR T cell–based therapies.

中文翻译：

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人类巨细胞病毒扩增 CD8+ T 细胞群，BCL11B 表达缺失，NK 细胞身份增加

CD8 ⁺ T 细胞不仅是适应性免疫的关键介质，而且可能表现出类似先天的特性，例如 NKG2C 的表面表达，NKG2C 是一种通常与自然杀伤 (NK) 细胞相关的激活受体。我们证明，与 NK 细胞类似，NKG2C ⁺ TCRαβ ⁺ CD8 ⁺ T 细胞与先前的人类巨细胞病毒 (HCMV) 暴露有关。除了表达几种 NK 细胞标志物，如 CD56 和 KIR，NKG2C ⁺ CD8 ⁺ T 细胞是寡克隆的，即使在持续激活时也不会上调 PD-1。此外，我们发现 NKG2C ⁺ CD8 ⁺一些个体的 T 细胞对白血病细胞和 HCMV 感染的成纤维细胞表现出强大的效应功能，这是由 NKG2C 和 TCR 特异性决定的。转录组学分析显示，与传统的 NKG2C ^- CD8 ^{+ T 细胞相比，转录因子}BCL11B是 T 细胞发育命运的调节因子，在 NKG2C ⁺ CD8 ⁺ T 细胞中下调。^{常规 CD8 + T 细胞中的}BCL11B缺失导致出现类似的先天样 CD56 ⁺ CD94 ⁺ DAP12 ⁺ NKG2C ⁺ CD45RA ⁺ CCR7 ^{-对 HLA-E +}靶具有活性的PD-1 ^{-/低T 细胞群。}基于其识别患病细胞的内在能力以及缺乏 PD-1 诱导，NKG2C ⁺ CD8 ⁺ T 细胞代表了位于先天免疫和适应性免疫之间边界的淋巴细胞群，为细胞治疗提供了一种有吸引力的替代方案，包括基于 CAR T 细胞的疗法。