Cytotoxic T-cell-mediated defense against infections in human liver transplant recipients
Cytotoxic T-cell-mediated defense against infections in human liver transplant recipients
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DOI：
10.1002/lt.21065
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发表时间：
2007-02-01
影响因子：
4.6
通讯作者：
Inaba, Kayo
中科院分区：
文献类型：
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作者：
Tanaka, Koichi;Uemoto, Shinji;Inaba, Kayo
以前的研究表明，术后感染是最高的移植受体与预先存在的高水平的细胞毒性T淋巴细胞（CTL）。为了研究这一现象，106例成人肝移植受者被分为3组，根据活体肝移植（LDLT）前CD 3（+）CD 8（+）CD 45亚型分数的分层聚类。组I具有最高的初始T细胞水平（亚群CD 45 RO（-）CCR 7（+）），组11具有最高的效应/记忆（EM）T细胞水平（亚群CD 45 RO（+）CCR 7（-）），组III具有最高的效应T细胞水平（亚群CD 45 RO（-）CCR 7（-））。在第1组中，CTL在对入侵病原体的反应中比其他组更早更快地上调;这种反应与CD 4（+）T细胞帮助、CD 27（+）CD 28（+）亚群下调以及干扰素-γ和穿孔素表达上调有关。相反，在组II和组III中，CTL在持续病毒感染后缓慢上调，并且对急性感染没有有效反应。此外，第II组的细胞溶解反应主要是由于上调的CD 8（-/-）EM T细胞部分，而第III组的细胞溶解反应是由于上调的效应T细胞。EM或效应T细胞的流行依赖于LDLT前CD 8（+）表型的分化。总之，在大多数死亡的感染移植受者中，CD 8（+）CTL的产生在没有相关的CD 4（+）T细胞帮助的情况下被抑制。
Previous studies have shown that postoperative infection is highest in transplant recipients with preexisting high levels of cytotoxic T lymphocytes (CTLs). To study this phenomenon, 106 adult liver transplant recipients were divided into 3 groups, based on hierarchical clustering of the CD3(+)CD8(+)CD45 isoform fractions prior to living donor liver transplantation (LDLT). Group I had the highest naive T-cell levels (subset CD45RO(-)CCR7(+)), Group 11 had the highest effector/memory (EM) T-cell levels (subset CD45RO(+)CCR7(-)), and Group III had the highest effector T-cell levels (subset CD45RO(-)CCR7(-)). In Group 1, CTLs upregulated in response to invading pathogens much earlier and more rapidly than the other groups; this response was associated with CD4(+) T-cell help, downregulation of CD27(+)CD28(+) subsets, and upregulation of interferon-gamma and perforin expression. In contrast, in Groups II and III, CTLs upregulated slowly following persistent viral infection and did not respond efficiently to acute infection. In addition, Group II's cytolytic responses were due mainly to upregulation of the CD8(-/-) EM T-cell fraction, whereas Group III's cytolytic responses were attributable to upregulation of effector T cells. The prevalence of EM or effector T cells was dependent on differentiation of the CD8(+) phenotype before LDLT. In conclusion, in most infected transplant recipients who died, generation of CD8(+) CTLs had been suppressed without associated CD4(+) T-cell help.