Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes
Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes
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DOI：
10.1111/j.1399-3089.2010.00575.x
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发表时间：
2010-05-01
影响因子：
3.9
通讯作者：
Ohdan, Hideki
中科院分区：
文献类型：
--
作者：
Tahara, Hiroyuki;Ide, Kentaro;Ohdan, Hideki
背景：目前公认，人T细胞对异种靶点的反应比对同种异体靶点的反应更强。然而，目前尚不清楚是否更有力的T细胞对异种抗原比同种异体抗原的反应是由于一个更高的频率或更强的反应的异种反应性T cells.Methods：我们确定的前体频率（PFs）和刺激指数（SI）的异种反应性人类T细胞进行混合淋巴细胞反应（MLR）测定使用羧基荧光素二乙酸琥珀酰亚胺酯（CFSE）标记技术。结果：异种反应性CD 4 + T细胞的SI显著高于同种异体反应性CD 4 + T细胞，而同种异体反应性和异种反应性CD 4 + T细胞前体的PF几乎相同，表明单个异种反应性CD 4 + T细胞的反应更强。相反，异种反应性CD 8 + T细胞的SI与同种异体反应性CD 4 + T细胞的SI没有差异，同种异体和异种反应性CD 8 + T细胞前体的PF也是相同的。在猪-人MLR试验中添加可溶性人CD 47-Fc融合蛋白导致异种反应性CD 4 + T细胞的SI在统计学上显著降低。在猪-人MLR试验中，通过进一步添加针对人CD 47或信号调节蛋白-α的阻断抗体（Ab）消除了这种改变。在此MLR检测中，从人类应答者PBMC群体中消耗非T细胞后添加人CD 47-Fc并不影响异种反应性CD 4 + T细胞的SI。结论：对异种抗原的T细胞反应比同种抗原更强烈，可能归因于异种反应性T细胞的反应更强; CD 47的种间不相容性可能通过间接途径促成这种异种反应性CD 4 + T细胞反应。
Background:It is acknowledged that the response of human T cells to xenogeneic targets is more potent than that to allogeneic targets. However, it is not clear whether the more vigorous T cell response to xenoantigens than to alloantigens is attributable to a higher frequency or stronger reaction of xenoreactive T cells.Methods:We determined the precursor frequencies (PFs) and stimulation indexes (SIs) of xenoreactive human T cells by performing a mixed lymphocyte reaction (MLR) assay using a carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique. Irradiated porcine or human peripheral blood mononuclear cells (PBMCs)used as stimulator cells-were cultured with CFSE-labeled human PBMCs-used as responder cells.Results:The SIs of the xenoreactive CD4+ T cells were significantly higher than those of the alloreactive CD4+ T cells, whereas the PFs of the alloreactive and xenoreactive CD4+ T cell precursors were almost identical, suggesting a stronger reaction by a single xenoreactive CD4+ T cell. In contrast, the SIs of the xenoreactive CD8+ T cells did not differ from those of the alloreactive CD4+ T cells, and the PFs of the allo- and xenoreactive CD8+ T cell precursors were also identical. Addition of a soluble human CD47-Fc fusion protein in the porcine-to-human MLR assay caused a statistically significant reduction of the SIs of the xenoreactive CD4+ T cells. Such an alteration was abrogated by further addition of blocking antibodies (Abs) against either human CD47 or signal regulatory protein-alpha in the porcine-to-human MLR assay. Addition of human CD47-Fc after the depletion of non-T cells from the population of human responder PBMCs in this MLR assay did not influence the SIs of the xenoreactive CD4+ T cells.Conclusions:The more vigorous T cell response to xenoantigens than to alloantigens is possibly attributable to a stronger reaction of xenoreactive T cells; the interspecies incompatibility of CD47 may contribute to such xenoreactive CD4+ T cell responses via an indirect pathway.