Imamura Masahiro
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Int J Hematol. 2002 Aug;76 Suppl 1:191-4. doi: 10.1007/BF03165243.
Analysis of cytokine gene expression in peripheral blood mononuclear cells from patients received allogeneic hematopoietic stem cells transplantation (allo-SCT) showed that type 1 helper T cells (Th1)-derived cytokines increased in severe graft-versus-host disease (GVHD) while Th2-derived cytokines such as IL-4, IL-10, and IL-13 increased in mild GVHD. These results indicate that Th2 cells suppress GVHD although Thl cells augment GVHD. Chimerism analysis showed that mixed chimerism was often observed in younger (<30 years old) patients. Mixed chimerism in older (> or = 30 years old) patients were related to rejection and relapse while this situation is not the case in younger patients, thus indicating that mixed chimerism is an important prognostic factor in older patients. Among the chimerism of various cell populations, donor-derived CD56-positive cells are important in early engraftment when determined in allogeneic nonmyeloablative stem cell transplantation (allo-NST), regardless of the proportion of donor-derived CD3-positive cells. This result suggests that donor-derived CD56-positive cells are a more useful indicator for engraftment and rejection in early time period. Complementary-determining region 3 (CDR3) size spectratyping in T-cell receptor (TCR) chain subfamilies (V beta) showed that high level of diversity in TCR V beta repertoire is important for a late rejection and skewed TCR V repertoire is well correlated to occurrence of GVHD. Expression of inhibitory natural killer (NK) cell receptors such as CD158b and CD94/NKG2A on peripheral CD3-negative and positive cells were increased in parallel with GVHD. Interestingly, these molecules appeared to regulate GVHD while preserving graft-versus-leukemia (GVL) effect.
对接受异基因造血干细胞移植（allo-SCT）患者外周血单个核细胞中细胞因子基因表达的分析表明，在严重移植物抗宿主病（GVHD）中，1型辅助性T细胞（Th1）衍生的细胞因子增加，而在轻度GVHD中，Th2衍生的细胞因子如白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和白细胞介素-13增加。这些结果表明，Th2细胞抑制GVHD，而Th1细胞增强GVHD。嵌合体分析显示，在年轻（<30岁）患者中常观察到混合嵌合体。年龄较大（≥30岁）患者中的混合嵌合体与排斥反应和复发有关，而年轻患者则不然，因此表明混合嵌合体是老年患者的一个重要预后因素。在异基因非清髓性干细胞移植（allo-NST）中确定各种细胞群体的嵌合体时，无论供体来源的CD3阳性细胞比例如何，供体来源的CD56阳性细胞在早期植入中都很重要。这一结果表明，供体来源的CD56阳性细胞是早期植入和排斥反应的更有用指标。T细胞受体（TCR）链亚家族（Vβ）中的互补决定区3（CDR3）大小谱型分析表明，TCR Vβ库的高度多样性对晚期排斥反应很重要，TCR V库的偏向与GVHD的发生密切相关。外周CD3阴性和阳性细胞上抑制性自然杀伤（NK）细胞受体如CD158b和CD94/NKG2A的表达与GVHD平行增加。有趣的是，这些分子似乎在调节GVHD的同时保留了移植物抗白血病（GVL）效应。
