Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood Adv. 2023 Oct 10;7(19):5784-5798. doi: 10.1182/bloodadvances.2022008952.
Cytomegalovirus (CMV) infection is associated with the expansion of a mature NKG2C+FcεR1γ- natural killer (NK) cell population. The exact mechanism underlying the emergence of NKG2C+ NK cells, however, remains unknown. Allogeneic hematopoietic cell transplantation (HCT) provides an opportunity to longitudinally study lymphocyte recovery in the setting of CMV reactivation, particularly in patients receiving T-cell-depleted (TCD) allografts. We analyzed peripheral blood lymphocytes from 119 patients at serial time points after infusion of their TCD allograft and compared immune recovery with that in samples obtained from recipients of T-cell-replete (T-replete) (n = 96) or double umbilical cord blood (DUCB) (n = 52) allografts. NKG2C+ NK cells were detected in 92% (45 of 49) of recipients of TCD HCT who experienced CMV reactivation. Although NKG2A+ cells were routinely identifiable early after HCT, NKG2C+ NK cells were identified only after T cells could be detected. T-cell reconstitution occurred at variable times after HCT among patients and predominantly comprised CD8+ T cells. In patients with CMV reactivation, recipients of TCD HCT expressed significantly higher frequencies of NKG2C+ and CD56neg NK cells compared with patients who received T-replete HCT or DUCB transplantation. NKG2C+ NK cells after TCD HCT were CD57+FcεR1γ+ and degranulated significantly more in response to target cells compared with the adaptive the NKG2C+CD57+FcεR1γ- NK cell population. We conclude that the presence of circulating T cells is associated with the expansion of a CMV-induced NKG2C+ NK cell population, a potentially novel example of developmental cooperation between lymphocyte populations in response to viral infection.
巨细胞病毒 (CMV) 感染与成熟 NKG2C+FcεR1γ-自然杀伤 (NK) 细胞群体的扩增有关。然而，NKG2C+NK 细胞出现的确切机制仍不清楚。异基因造血细胞移植 (HCT) 为研究 CMV 再激活背景下淋巴细胞恢复提供了机会，尤其是在接受 T 细胞耗竭 (TCD) 同种异体移植的患者中。我们分析了 119 例患者在输注 TCD 同种异体移植物后的连续时间点的外周血淋巴细胞，并将免疫恢复与接受 T 细胞丰富 (T-replete) (n=96) 或双脐血 (DUCB) (n=52) 同种异体移植的受者的样本进行了比较。在经历 CMV 再激活的 TCD HCT 受者中，92%（45/49）检测到 NKG2C+NK 细胞。尽管在 HCT 后早期通常可以识别 NKG2A+细胞，但只有在可以检测到 T 细胞后才能识别 NKG2C+NK 细胞。HCT 后，不同患者的 T 细胞重建发生在不同时间，主要由 CD8+T 细胞组成。在发生 CMV 再激活的患者中，与接受 T-replete HCT 或 DUCB 移植的患者相比，TCD HCT 受者表达的 NKG2C+和 CD56neg NK 细胞频率明显更高。与适应性 NKG2C+CD57+FcεR1γ- NK 细胞群体相比，TCD HCT 后产生的 NKG2C+NK 细胞 CD57+FcεR1γ+，并对靶细胞显著脱颗粒。我们得出结论，循环 T 细胞的存在与 CMV 诱导的 NKG2C+NK 细胞群体的扩增有关，这是淋巴细胞群体对病毒感染作出反应的发育性合作的潜在新实例。
