Chen Benny J, Deoliveira Divino, Cui Xiuyu, Le Ngocdiep T, Son Jessica, Whitesides John F, Chao Nelson J
Division of Cellular Therapy/Bone Marrow Transplantation, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Blood. 2007 Apr 1;109(7):3115-23. doi: 10.1182/blood-2006-04-016410.
Several groups, including our own, have independently demonstrated that effector memory T cells from non-alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells, and we studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent than bulk T cells in mediating GVHD. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed-lymphocyte cultures. However, the proliferative responses of memory T cells were more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2-secreting cells measured by 42-hour enzyme-linked immunosorbent spot (ELISPOT) assay were similar among naive, memory, and bulk T cells. These data indicated that memory T cells are able to respond to alloantigens initially but fail to develop to full potential. The abortive immune response, which was mediated by non-alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non-alloantigen-primed donors could not induce GVHD.
包括我们自己的研究小组在内的几个团队已经独立证明，来自未接受过同种异体抗原刺激的供体的效应记忆T细胞不会引发移植物抗宿主病（GVHD）。在当前的研究中，我们进一步研究了这种方法是否可以扩展到所有记忆T细胞，并研究了其潜在机制。无论是总记忆T细胞还是纯化的中枢记忆T细胞都无法诱导GVHD。在介导GVHD方面，记忆T细胞的效力比大量T细胞至少低3个对数。正如预期的那样，在标准的5天混合淋巴细胞培养中，记忆T细胞未能引发细胞毒性，并且对同种异体抗原的增殖能力较差。然而，当缩短培养时间时，记忆T细胞的增殖反应与大量T细胞和幼稚T细胞的增殖反应更具可比性。此外，通过42小时酶联免疫吸附斑点（ELISPOT）测定法测量的白细胞介素-2分泌细胞的频率在幼稚T细胞、记忆T细胞和大量T细胞中相似。这些数据表明，记忆T细胞能够最初对同种异体抗原作出反应，但无法充分发挥其潜力。由非同种异体抗原特异性记忆T细胞对同种异体抗原介导的流产免疫反应，可能解释了为什么来自未致敏和未接受过同种异体抗原刺激的供体的记忆T细胞不能诱导GVHD。
