Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease
Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease
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DOI：
10.1182/blood.v98.7.2256
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发表时间：
2001-10-01
期刊：
影响因子：
20.3
通讯作者：
van den Brink, MRM
中科院分区：
文献类型：
--
作者：
Alpdogan, O;Schmaltz, C;van den Brink, MRM
异基因骨髓移植（BMT）后持续的免疫缺陷会导致感染的发病率和死亡率显着增加。本研究在小鼠模型中研究了白细胞介素-7（IL-7）对主要组织相容性复合体（MHC）匹配或不匹配的异基因骨髓移植的年轻和中年（9个月大）受者的影响。虽然同基因骨髓移植后第0 ~ 14天给予IL-7可促进淋巴重建，但该方案在异基因骨髓移植后无效。然而，IL-7的管理，从第14天（或21）至27天后，同种异体骨髓移植加速恢复的主要淋巴细胞群体，即使在中年受者。该方案显著扩增了供体来源的胸腺细胞和外周T细胞、骨髓和脾中的B系细胞、脾自然杀伤（NK）细胞、NK T细胞以及单核细胞和巨噬细胞。有趣的是，虽然接受IL-7治疗的受者在CD 4（+）和CD 8（+）记忆T细胞群体中有显著增加，但幼稚T细胞的增加不太明显。然而，最值得注意的是观察到IL-7治疗不会加重MHC匹配BMT受体中的移植物抗宿主病（GVHD），并且会改善MHC不匹配BMT受体中的GVHD。尽管如此，移植物抗白血病（GVL）活性（针对32 Dp 210白血病测量）保持完整。虽然活化和记忆性CD 4+和CD 8 + T细胞通常表达高水平的IL-7受体（IL-7 R，CD 127），但来自同种异体BMT受体的活化和记忆性同种异体反应性供体来源的T细胞表达很少的IL-7 R。这可能解释了IL-7给药未能加重GVHD。总之，移植后给予异基因BMT受体IL-7可增强淋巴重建，而不加重GVHD，同时保留GVL。(C)2001年，美国血液学会。
Prolonged Immunodeficiency after allogeneic bone marrow transplantation (BMT) causes significant morbidity and mortality from infection. This study examined In murine models the effects of Interleukin-7 (IL-7) given to young and middle-aged (9-month-old) recipients of major histocompatibility complex (MHC)-matched or -mismatched allogeneic BMT. Although administration of IL-7 from day 0 to 14 after syngeneic BMT promoted lymphoid reconstitution, this regimen was ineffective after allogeneic BMT. However, IL-7 administration from day 14 (or 21) to 27 after allogeneic BMT accelerated restoration of the major lymphoid cell populations even in middle-aged recipients. This regimen significantly expanded donor-derived thymocytes and peripheral T cells, B-lineage cells In bone marrow and spleen, splenic natural killer (NK) cells, NK T cells, and monocytes and macrophages. Interestingly, although recipients treated with IL-7 had significant Increases in CD4(+) and CD8(+) memory T-cell populations, Increases In naive T cells were less profound. Most notable, however, were the observations that IL-7 treatment did not exacerbate graft-versus-host disease (GVHD) in recipients of an MHC-matched BMT, and would ameliorate GVHD in recipients of a MHC-mismatched BMT. Nonetheless, graft-versus-leukemia (GVL) activity (measured against 32Dp210 leukemia) remained intact. Although activated and memory CD4+ and CD8+ T cells normally express high levels of IL-7 receptor (IL-7R, CD127), activated and memory alloreactive donor-derived T cells from recipients of allogeneic BMT expressed little IL-7R. This might explain the failure of IL-7 administration to exacerbate GVHD. In conclusion, posttransplant IL-7 administration to recipients of an allogeneic BMT enhances lymphoid reconstitution without aggravating GVHD while preserving GVL. (C) 2001 by The American Society of Hematology.