Chen Benny J, Cui Xiuyu, Sempowski Gregory D, Liu Congxiao, Chao Nelson J
Bone Marrow Transplantation Program, Department of Medicine, Human Vaccine Institute, Duke University Medical Center, 2400 Pratt St, Ste 1100, Box 3961, Durham, NC 27705, USA.
Blood. 2004 Feb 15;103(4):1534-41. doi: 10.1182/blood-2003-08-2987. Epub 2003 Oct 9.
The major challenge in allogeneic hematopoietic cell transplantation is how to transfer allogeneic T-cell immunity without causing graft-versus-host disease (GVHD). Here we report a novel strategy to selectively prevent GVHD by depleting CD62L(+) T cells (naive and a subset of memory T cells). In unprimed mice, CD62L(-) T cells (a subset of memory T cells) failed to proliferate in response to alloantigens (which the mice have never previously encountered) and were unable to induce GVHD in allogeneic hosts. CD62L(-) T cells contributed to T-cell reconstitution by peripheral expansion as well as by promoting T-cell regeneration from bone marrow stem/progenitor cells. CD62L(-) T cells from the animals previously primed with a tumor cell line (BCL1) were able to inhibit the tumor growth in vivo but were unable to induce GVHD in the third-party recipients. This novel technology may allow transfer of allogeneic recall antitumor and antimicrobial immunity without causing GVHD.
异基因造血细胞移植的主要挑战在于如何传递异基因T细胞免疫而不引发移植物抗宿主病(GVHD)。在此,我们报告一种通过清除CD62L(+) T细胞(初始T细胞和一部分记忆T细胞)来选择性预防GVHD的新策略。在未致敏的小鼠中,CD62L(-) T细胞(一部分记忆T细胞)对同种异体抗原(小鼠此前从未接触过)无增殖反应,且无法在异基因宿主体内诱导GVHD。CD62L(-) T细胞通过外周扩增以及促进骨髓干/祖细胞的T细胞再生,对T细胞重建有贡献。来自先前用肿瘤细胞系(BCL1)致敏的动物的CD62L(-) T细胞能够在体内抑制肿瘤生长,但无法在第三方受体中诱导GVHD。这项新技术可能允许传递异基因回忆性抗肿瘤和抗微生物免疫,而不引发GVHD。