Freedman M S, Blain M, Antel J P
Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Québec, Canada.
Cell Immunol. 1991 Apr 1;133(2):306-16. doi: 10.1016/0008-8749(91)90106-l.
To examine whether functionally different CD4+ cells respond uniformly to the immunoregulatory influences of allogeneic activated CD8+ cells (*CD8+), we subfractionated the CD4+ population into two subsets, based on the high expression of either CD45RA or CD29. We confirmed that the CD45RA+ cells proliferated poorly in response to soluble anti-CD3 mAb, compared to the vigorous response obtained with the CD29+ subset; the CD45RA+ cells were more responsive to stimulation with Con A. Using normal healthy controls, we found that whereas *CD8+ had a significant suppressive effect on the proliferation of the CD29+ subset, they augmented the mitogen-induced proliferative response of the CD45RA+ cells. We further demonstrated that *CD8+ derived from MS patients augmented the response of the CD45RA+ subset to a significantly higher degree compared to healthy age- and sex-matched controls. There were no significant differences between the degree of suppression exerted by the *CD8+ of either the MS or the control group on the CD29+ cells. These results demonstrate that helper/memory CD4+CD29+ cells are more sensitive to the suppressive influences of *CD8+ compared to the CD4+CD45RA+ subset. In addition, in MS, *CD8+ may contribute to a more pronounced "on" signal for virgin CD4+CD45RA+ cells, which might serve as a means to perpetuate the autoimmune disease process.
为了研究功能不同的CD4+细胞对同种异体活化CD8+细胞（CD8+）的免疫调节影响是否有一致的反应，我们根据CD45RA或CD29的高表达将CD4+群体细分为两个亚群。我们证实，与CD29+亚群获得的强烈反应相比，CD45RA+细胞对可溶性抗CD3单克隆抗体的反应增殖较差；CD45RA+细胞对刀豆蛋白A的刺激反应更强。使用正常健康对照，我们发现CD8+对CD29+亚群的增殖有显著抑制作用，而它们增强了CD45RA+细胞的丝裂原诱导增殖反应。我们进一步证明，与年龄和性别匹配的健康对照相比，来自MS患者的CD8+对CD45RA+亚群反应的增强程度明显更高。MS组或对照组的CD8+对CD29+细胞施加的抑制程度没有显著差异。这些结果表明，与CD4+CD45RA+亚群相比，辅助/记忆性CD4+CD29+细胞对*CD8+的抑制影响更敏感。此外，在MS中，*CD8+可能有助于为原始CD-4+CD45RA+细胞提供更明显的“开启”信号，这可能是使自身免疫疾病过程持续存在的一种方式。
