Influence of T cell depletion method on circulating γδ T cell reconstitution and potential role in the graft-versus-leukemia effect
Influence of T cell depletion method on circulating γδ T cell reconstitution and potential role in the graft-versus-leukemia effect
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DOI：
10.1080/0032472031000141295
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发表时间：
1999-01-01
期刊：
影响因子：
4.5
通讯作者：
Henslee-Downey, PJ
中科院分区：
文献类型：
--
作者：
Lamb, LS;Gee, AP;Henslee-Downey, PJ
背景我们实验室以前报道过，接受部分不匹配的亲属供者（PMRD）的抗TCR α β T细胞耗竭（TCD）移植后的前6个月内产生大于或等于10% γ δ（+）T细胞的白血病患者具有无病生存（DFS）优势。这些γ δ（+）T细胞是V δ 1（+）CD 3（+）CD 4（-）CD 8（-）CD 69（+）HLADR（+），并且对K562细胞具有细胞毒性。我们接受了使用抗TCR α β单克隆抗体T10 B 9 - 1A 31的TCD PMRD移植物的患者的γ δ（+）T细胞的TCD PMRD移植物结果43例T10 B 9 TCD患者中有10例出现细胞毒性V δ 1（+）T细胞增加，而OKT 3 TCP组中有7例出现细胞毒性V δ 1（+）T细胞增加（23%vs7%，p = 0.010）。与OKT 3患者相比，具有增加的γ δ（+）T细胞的T10 B 9患者也表现出更高范围的增加的γ δ（+）T细胞，并且γ δ（+）T细胞保持高水平的时间长度更长。具有增加的γ δ（+）T细胞的患者，其移植物是T细胞耗尽的T细胞，其复发率显著降低（p = 0.038）。在OKT 3 TCD患者中观察到类似的复发率和复发率降低，尽管由于γ δ（+）T细胞增加的患者数量较少而未达到显著性。γ δ（+）T细胞增加的T10 B 9患者的估计3年无病生存率显著提高（0.79 vs 0.31，p = 0.009），在OKT 3患者中也观察到这一趋势（p = 0.091）.讨论这些观察结果表明V δ 1（+）CD 4（-）Cd 8（-）细胞毒性T细胞与较低的复发率和改善的存活率相关，因此可能在移植物抗白血病效应中起作用。
BackgroundOur laboratory previously reported that leukemia patients who developed greater than or equal to 10% gamma delta(+) T cells during the first six-months after receiving an anti-TCR alpha beta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gamma delta(+) T cells were V delta 1(+)CD3(+)CD4(-)CD8(-)CD69(+)HLADR(+) and are cytotoxic to K562 cells.MethodsIn order to determine wheather the anti-alpha beta TCD regimen was associated with these findings, we recieved TCD PMRD grafts using gamma delta(+) T cells from patients who recieved TCD PMRD grafts using the anti-TCR alpha beta MAb T10B9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3.ResultsIncreased cytotoxic V delta 1(+) T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCP group (23% versus 7%, p = 0.010). T10B9 patients with incresed gamma delta(+) T cells also exhibited a higher range of increased gamma delta(+) T cells and the length of time the gamma delta(+) T cells remained high was longer when compared to OKT3 patients. Patients with increased gamma delta(+) T cells whose grafts were T-cell depleted with T-cell showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significant was not reached due to the small number of patients with increased gamma delta(+) T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gamma delta(+) T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091).DiscussionThese observations indicate that V delta 1(+)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.