Zhang Yi, Joe Gerard, Zhu Jiang, Carroll Richard, Levine Bruce, Hexner Elizabeth, June Carl, Emerson Stephen G
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Blood. 2004 May 15;103(10):3970-8. doi: 10.1182/blood-2003-09-3135. Epub 2004 Feb 5.
Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8(+) T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44(hi)CD8(+) effector/memory T cells were functionally defective in inducing GVHD, whereas CD44(lo)CD8(+) naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44(lo)CD8(+) T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44(lo)CD8(+) T cells, CD44(hi)CD8(+) T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8(+) T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.
移植物抗宿主病（GVHD）由宿主抗原呈递细胞（APC）触发，这些细胞激活供体T细胞增殖和分化，但尚不清楚是哪些APC激活的供体T细胞亚群介导了GVHD与有益的抗肿瘤效应。利用人GVHD的CD8(+) T细胞依赖性小鼠模型，我们发现宿主树突状细胞（DC）诱导的CD44(hi)CD8(+)效应/记忆T细胞在诱导GVHD方面功能缺陷，而CD44(lo)CD8(+)幼稚表型T细胞是极强的GVHD诱导剂。移植前从宿主DC刺激的T细胞中去除CD44(lo)CD8(+) T细胞可预防GVHD，而不损害其体内抗肿瘤活性。与CD44(lo)CD8(+) T细胞相比，CD44(hi)CD8(+) T细胞表达高水平的Fas，并在移植后在体内被有效清除。这些结果表明，体外同种异体DC刺激供体CD8(+) T细胞可能有助于预防GVHD并优化体内抗肿瘤治疗。
