Background Our laboratory previously reported that leukemia patients who developed ≥ 10% γδ + T cells during the first six months after receiving an anti-TCRαβ T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These γδ + T cells were Vδ1 + CD3 + CD4 − CD8 − CD69 + HLADR + and are cytotoxic to K562 cells. Methods In order to determine whether the anti-αβ TCD regimen was associated with these findings, we compared the reconstitution of γδ + T cells from patients who received TCD PMRD grafts using the anti-TCRαβ MAb T10B9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3. Results Increased cytotoxic Vδ1 + T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCD group (23% versus 7%, p=0.010). T10B9 patients with increased γδ + T cells also exhibited a higher range of increased γδ + T cells and the length of time the γδ + T cells remained high was longer when compared to OKT3 patients. Patients with increased γδ + T cells whose grafts were T-cell depleted with T10B9 showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significance was not reached due to the small number of patients with increased γδ + T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased γδ + T cells (0.79 versus 0.31, p=0.009), a trend also seen in OKT3 patients (p = 0.091). Discussion These observations indicate that Vδ1 + CD4 − CD8 − cytotoxic T cells are associated with lower relapse rates and improved survival, and thus may have a role in a graft-versus-leukemia effect.

中文翻译：

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T 细胞耗竭方法对循环 γδ T 细胞重建的影响和在移植物抗白血病效应中的潜在作用

背景 我们的实验室之前曾报道，在接受来自部分不匹配相关供体 (PMRD) 的抗 TCRαβ T 细胞耗竭 (TCD) 移植物后的前六个月内，出现≥ 10% γδ + T 细胞的白血病患者患有疾病——自由生存（DFS）优势。这些γδ + T 细胞是 Vδ1 + CD3 + CD4 - CD8 - CD69 + HLADR + 并且对 K562 细胞具有细胞毒性。方法为了确定抗αβ TCD 方案是否与这些发现相关，我们比较了使用抗 TCRαβ MAb T10B9-1A31（先前报道）接受 TCD PMRD 移植的患者的 γδ + T 细胞与类似患者的重建谁接受了使用抗 CD3 MAb OKT3 的移植物。结果 在 43 名 T10B9 TCD 患者中的 10 名中观察到细胞毒性 Vδ1 + T 细胞增加，而在 OKT3 TCD 组中则为 100 名中的 7 名（23% 对 7%，p=0.010）。与 OKT3 患者相比，具有增加的 γδ + T 细胞的 T10B9 患者也表现出更大范围的 γδ + T 细胞增加，并且 γδ + T 细胞保持高水平的时间长度更长。具有增加的 γδ + T 细胞的患者，其移植物是 T10B9 耗尽的 T 细胞，复发率显着降低（p = 0.038）。在 OKT3 TCD 患者中观察到类似的比率和复发率降低，但由于 γδ + T 细胞增加的患者数量较少，因此未达到显着性。γδ + T 细胞增加的 T10B9 患者的估计 3 年无病生存率显着提高（0.79 对 0.31，p = 0.009），OKT3 患者中也有这种趋势（p = 0.091）。讨论 这些观察结果表明 Vδ1 + CD4 - CD8 - 细胞毒性 T 细胞与较低的复发率和提高的存活率有关，