Levy R B, Jones M, Cray C
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
J Immunol. 1990 Dec 15;145(12):3998-4005.
Graft-vs-host reactions (GvHR) following the injection of class I/II MHC disparate parental cells into unirradiated F1 recipient mice result in the development of marked immune dysfunction. Following negative selection using adherence and antibody and complement depletion, highly purified T cells were examined to determine their ability to undergo activation. Three weeks after GvHR initiation, unstimulated splenic T cells from GvHR mice displayed normal CD3 and IL-2R expression but elevated expression of class I MHC and Ly-6A/E antigens. Despite culture with normal F1 accessory cells, both CD4+ and CD8+ GvHR T cells exhibited low levels of proliferation to both Con A and anti-CD3 mAb. Although following exposure for 12 h to either of these stimuli, GvHR T cells expressed normal levels of IL-2R, expression was greatly decreased vs normal T cells between 24 and 48 h. In addition, at no timepoint was detectable IL-2 produced by GvHR T cells. Importantly, mixing experiments did not demonstrate detectable suppressive activity in the purified GvHR T cell subsets. GvHR T cells were also tested for their ability to respond to stimuli in the absence of any accessory cell population. These cells again did not proliferate to levels equivalent to normal T cells. Incubation with PMA and either cytokines (Con A supernatant, rIL-7) or anti-CD3 mAb resulted in only low levels of proliferation in GvHR T cells. Notably, at high ionomycin concentrations together with PMA, GvHR T cells did proliferate to equivalent levels as normal cells. However, with decreasing concentrations of ionophore, these cells failed to proliferate as well as normal cells. In total, these findings demonstrate that GvHR T cells are phenotypically and functionally distinct from normal T cells. The results suggest that GvHR T cells themselves may contribute to the well-characterized immune depression occurring in recipients undergoing GvHR.
将I/II类主要组织相容性复合体（MHC）不相容的亲代细胞注射到未受照射的F1受体小鼠体内后，移植物抗宿主反应（GvHR）会导致明显的免疫功能障碍。在使用贴壁法以及抗体和补体去除法进行阴性选择后，对高度纯化的T细胞进行检测，以确定它们的激活能力。GvHR开始三周后，来自GvHR小鼠的未受刺激的脾T细胞显示出正常的CD3和IL-2R表达，但I类MHC和Ly-6A/E抗原的表达升高。尽管与正常的F1辅助细胞一起培养，CD4+和CD8+ GvHR T细胞对刀豆蛋白A（Con A）和抗CD3单克隆抗体（mAb）的增殖水平均较低。虽然在暴露于这两种刺激之一12小时后，GvHR T细胞表达正常水平的IL-2R，但在24至48小时之间，其表达与正常T细胞相比大幅下降。此外，在任何时间点，GvHR T细胞都未检测到产生IL-2。重要的是，混合实验未在纯化的GvHR T细胞亚群中显示出可检测到的抑制活性。还测试了GvHR T细胞在没有任何辅助细胞群体的情况下对刺激作出反应的能力。这些细胞再次未能增殖到与正常T细胞相当的水平。用佛波酯（PMA）与细胞因子（Con A上清液、重组白细胞介素-7（rIL-7））或抗CD3 mAb一起孵育，导致GvHR T细胞仅出现低水平的增殖。值得注意的是，在高浓度离子霉素与PMA共同作用下，GvHR T细胞确实能增殖到与正常细胞相当的水平。然而，随着离子载体浓度的降低，这些细胞的增殖能力不如正常细胞。总的来说，这些发现表明GvHR T细胞在表型和功能上与正常T细胞不同。结果表明，GvHR T细胞本身可能导致接受GvHR的受体中出现的特征性免疫抑制。
