Lamb L S, Gee A P, Hazlett L J, Musk P, Parrish R S, O'Hanlon T P, Geier S S, Folk R S, Harris W G, McPherson K, Lee C, Henslee-Downey P J
Division of Transplantation Medicine, Palmetto Richland Memorial Hospital, Center for Cancer Treatment and Research, University of South Carolina School of Medicine, Columbia, South Carolina 29203, USA.
Cytotherapy. 1999;1(1):7-19. doi: 10.1080/0032472031000141295.
Our laboratory previously reported that leukemia patients who developed > or = 10% gammadelta+ T cells during the first six months after receiving an anti-TCRalphabeta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gammadelta+ T cells were V81+CD3+CD4-CD8-CD69+HLADR+ and are cytotoxic to K562 cells.
In order to determine whether the anti-alphabeta TCD regimen was associated with these findings, we compared the reconstitution of gammadelta+ T cells from patients who received TCD PMRD grafts using the anti-TCRc4 MAb TIOB9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3.
Increased cytotoxic Vdelta1+ 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 gammadelta+ T cells also exhibited a higher range of increased gammadelta+ T cells and the length of time the gammadelta+ T cells remained high was longer when compared to OKT3 patients. Patients with increased gammadelta+ 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 gammadelta+ T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gammadelta+ T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091).
These observations indicate that Vdelta1+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.
我们实验室先前报道，接受部分不匹配相关供体（PMRD）的抗TCRαβ T细胞去除（TCD）移植物后的头六个月内，γδ+ T细胞比例升高至≥10%的白血病患者具有无病生存（DFS）优势。这些γδ+ T细胞为V81+CD3+CD4-CD8-CD69+HLADR+，对K562细胞具有细胞毒性。
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TCRc4单克隆抗体TIOB9-1A31（先前报道）接受TCD PMRD移植物的患者与使用抗CD3单克隆抗体OKT3接受移植物的类似患者中γδ+ T细胞的重建情况。
43例T10B9 TCD患者中有10例出现细胞毒性Vδ1+ T细胞增加，而OKT3 TCD组100例中有7例出现增加（23%对7%，p = 0.010）。与OKT3患者相比，γδ+ T细胞增加的T10B9患者γδ+ T细胞增加的范围也更高，且γδ+ T细胞保持高水平的时间更长。移植物用T10B9去除T细胞且γδ+ T细胞增加的患者复发率显著降低（p = 0.038）。OKT3 TCD患者中也观察到类似的复发率和降低情况，尽管由于γδ+ T细胞增加的患者数量较少未达到统计学显著性。γδ+ T细胞增加的T10B9患者估计3年无病生存率显著提高（0.79对0.31，p = 0.009），OKT3患者中也有此趋势（p = 0.091）。
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改善的生存率相关，因此可能在移植物抗白血病效应中发挥作用。
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