Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells
Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells
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DOI：
10.1182/blood-2007-09-107953
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发表时间：
2008-05-15
期刊：
影响因子：
20.3
通讯作者：
Shlomchik, Mark J.
中科院分区：
文献类型：
--
作者：
Anderson, Britt E.;Taylor, Patricia A.;Shlomchik, Mark J.
移植物抗宿主病(GVHD)仍然是异基因干细胞移植中发病率和死亡率的主要原因。效应记忆T细胞(T-EM)不会引起移植物抗宿主病(GVHD)，而是植入和装载免疫反应，包括移植物抗肿瘤效应。T-EM不能引起GVHD的一个可能的解释是T-EM缺乏CD62L和CCR7，CD62L和CCR7是引导原始T细胞(T-N)到淋巴(LN)和Peyer斑块(PP)的工具，这两个部位可能是GVHD的起始部位。因此，T-EM应该相对排除在LN和PP之外，这可能是它们不能引起GVHD的原因。我们用缺乏CD62L或CCR7的T细胞、缺乏CD62L的Pnad配体的移植受者以及没有LN和PP或LN、PP和脾的受者验证了这一假设。令人惊讶的是，CD62L和CCR7不是T-N介导的GVHD所必需的。此外，在多株配对中，缺乏LN和PP的受者会发生移植物抗宿主病。缺乏主要次级淋巴组织(SLT)的小鼠甚至可以诱发轻度GVHD。相反，T-EM上强制表达CD62L并不能使其具有引起移植物抗宿主病的能力。综上所述，这些数据驳斥了T-EM未能诱导GVHD是因为向LN和PP的低效转运的假设。
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation. Effector memory T cells (T-EM) do not cause GVHD but engraft and mount immune responses, including graft-versus-tumor effects. One potential explanation for the inability of T-EM to cause GVHD is that T-EM lack CD62L and CCR7, which are instrumental in directing naive T cells (T-N) to lymph nodes (LN) and Peyer patches (PP), putative sites of GVHD initiation. Thus T-EM should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN and PP or LN, PP, and spleen. Surprisingly, CD62L and CCR7 were not required for T-N-mediated GVHD. Moreover, in multiple strain pairings, GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on T-EM did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that T-EM fail to induce GVHD because of inefficient trafficking to LN and PP.