Yamashita Kouhei, Choi Uimook, Woltz Patricia C, Foster Susan F, Sneller Michael C, Hakim Francis T, Fowler Daniel H, Bishop Michael R, Pavletic Steven Z, Tamari Marisa, Castro Kathleen, Barrett A John, Childs Richard W, Illei Gabor G, Leitman Susan F, Malech Harry L, Horwitz Mitchell E
Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-1886, USA.
Blood. 2004 May 15;103(10):3986-8. doi: 10.1182/blood-2003-09-3286. Epub 2004 Feb 5.
Donor alloreactive CD4(+) T cells are important to the pathogenesis of chronic graft-versus-host disease (cGVHD), but specific subsets of CD4(+) T cells responsible for GVHD have not been defined. We hypothesized that cGVHD might be associated with a preponderance of CD4(+) effector memory cells (CCR7(-)/CD62L(low), CD4(EM)). We analyzed CCR7 and CD62L expression on CD4(+) T cells from stem cell transplantation patients, who did or did not develop cGVHD, and healthy donors. Patients with cGVHD had a higher percentage of CD4(EM) cells (35.5% +/- 2.9%) than healthy donors (13.8% +/- 0.7%; P <.0001) or patients without cGVHD that received a transplant (21.7% +/- 2.1%; P <.01). Using corticosteroid dose as a surrogate marker for cGVHD severity, severe cGVHD was associated with a higher percentage of CD4(EM) cells. The proportion of CD4(EM) cells in corticosteroid-dependent patients with systemic lupus erythematosis or Wegener granulomatosis did not differ from patients without cGVHD that received a transplant. This finding implies that overrepresentation of CD4(EM) cells is a unique feature of cGVHD.
供体同种异体反应性CD4(+) T细胞对慢性移植物抗宿主病（cGVHD）的发病机制很重要，但负责移植物抗宿主病的CD4(+) T细胞的特定亚群尚未明确。我们推测cGVHD可能与CD4(+)效应记忆细胞（CCR7(-)/CD62L(低)，CD4(EM)）占优势有关。我们分析了干细胞移植患者（无论是否发生cGVHD）以及健康供体的CD4(+) T细胞上CCR7和CD62L的表达。发生cGVHD的患者中CD4(EM)细胞的百分比（35.5% +/- 2.9%）高于健康供体（13.8% +/- 0.7%；P <.0001）或未发生cGVHD的移植患者（21.7% +/- 2.1%；P <.01）。使用皮质类固醇剂量作为cGVHD严重程度的替代标志物，重度cGVHD与更高百分比的CD4(EM)细胞相关。患有系统性红斑狼疮或韦格纳肉芽肿病的皮质类固醇依赖患者中CD4(EM)细胞的比例与未发生cGVHD的移植患者没有差异。这一发现表明CD4(EM)细胞的过度存在是cGVHD的一个独特特征。
