University of Calgary/Alberta Health Services, Calgary, Alberta, Canada.
Cytotherapy. 2012 Nov;14(10):1258-75. doi: 10.3109/14653249.2012.715243. Epub 2012 Sep 18.
Anti-thymocyte globulin (ATG) is being used increasingly to prevent graft-versus-host disease (GvHD); however, its impact on immune reconstitution is relatively unknown. We (i) studied immune reconstitution after ATG-conditioned hematopoietic cell transplantation (HCT), (ii) determined the factors influencing the reconstitution, and (iii) compared it with non-ATG-conditioned HCT.
Immune cell subset counts were determined at 1-24 months post-transplant in 125 HCT recipients who received ATG during conditioning. Subset counts were also determined in 46 non-ATG-conditioned patients (similarly treated).
(i) Reconstitution after ATG-conditioned HCT was fast for innate immune cells, intermediate for B cells and CD8 T cells, and very slow for CD4 T cells and invariant natural killer T (iNKT) (iNKT) cells. (ii) Faster reconstitution after ATG-conditioned HCT was associated with a higher number of cells of the same subset transferred with the graft in the case of memory B cells, naive CD4 T cells, naive CD8 T cells, iNKT cells and myeloid dendritic cells; lower recipient age in the case of naive CD4 T cells and naive CD8 T cells; cytomegalovirus recipient seropositivity in the case of memory/effector T cells; an absence of GvHD in the case of naive B cells; lower ATG serum levels in the case of most T-cell subsets, including iNKT cells; and higher ATG levels in the case of NK cells and B cells. (iii) Compared with non-ATG-conditioned HCT, reconstitution after ATG-conditioned HCT was slower for CD4 T cells, and faster for NK cells and B cells.
ATG worsens the reconstitution of CD4 T cells but improves the reconstitution of NK and B cells.
抗胸腺细胞球蛋白（ATG）越来越多地用于预防移植物抗宿主病（GvHD）；然而，其对免疫重建的影响相对未知。我们：（i）研究了 ATG 预处理造血细胞移植（HCT）后的免疫重建，（ii）确定了影响重建的因素，（iii）并将其与非 ATG 预处理 HCT 进行了比较。
在接受 ATG 预处理的 125 例 HCT 受者中，在移植后 1-24 个月测定免疫细胞亚群计数。还在 46 例非 ATG 预处理患者（同样治疗）中测定了亚群计数。
（i）ATG 预处理 HCT 后，固有免疫细胞的重建较快，B 细胞和 CD8 T 细胞的重建中等，CD4 T 细胞和固有自然杀伤 T（iNKT）细胞的重建非常缓慢。（ii）ATG 预处理 HCT 后更快的重建与以下因素相关：移植时同种细胞亚群的细胞数量更多，例如记忆 B 细胞、幼稚 CD4 T 细胞、幼稚 CD8 T 细胞、iNKT 细胞和髓样树突状细胞；幼稚 CD4 T 细胞和幼稚 CD8 T 细胞的受体年龄较低；受者巨细胞病毒血清阳性的记忆/效应 T 细胞；无 GvHD 的幼稚 B 细胞；大多数 T 细胞亚群（包括 iNKT 细胞）的血清 ATG 水平较低；NK 细胞和 B 细胞的 ATG 水平较高。（iii）与非 ATG 预处理 HCT 相比，ATG 预处理 HCT 后 CD4 T 细胞的重建较慢，NK 细胞和 B 细胞的重建较快。
ATG 可加重 CD4 T 细胞的重建，但可改善 NK 和 B 细胞的重建。
