Sobel E S, Yokoyama W M, Shevach E M, Eisenberg R A, Cohen P L
Department of Medicine, University of North Carolina, Chapel Hill 27599.
J Immunol. 1993 Jan 15;150(2):673-82.
MRL/Mp-lpr/lpr (MRL/lpr) mice develop marked lymphadenopathy, characterized predominantly by Thy1+CD3+CD4-CD8- cells ("double negative T cells"; DNT). It is paradoxical that DNT proliferate poorly in vitro when stimulated through CD3 or by mitogens. The hamster mAb H1.2F3, raised against dendritic epidermal DNT, recognizes a very early activation (VEA) Ag, which is generally absent on resting cells but expressed soon after T cell activation with ConA or phorbol ester. Cross-linking of this disulfide-linked dimer in the presence of APC and phorbol ester induces proliferation of normal T cells. Therefore, we tested to see whether MRL/lpr DNT expressed this Ag and whether it might play a role in DNT expansion. Unmanipulated cells from enlarged MRL/lpr lymph nodes expressed VEA in an age-dependent manner, peaking at 3 to 4 mo of age. Only limited expression in a small subset of lymphocytes from the congenic MRL/Mp(-)+/+ strain was seen. VEA expression on freshly harvested MRL/lpr lymphocytes was seen mainly on DNT, yet double staining of the DNT for VEA Ag and three other markers known to be present on lpr DNT showed that the DNT were a heterogeneous population. In addition, some CD4+ T cells expressed VEA Ag. Despite their constitutive VEA Ag expression, MRL/lpr DNT showed no proliferative response to cross-linking with the H1.2F3 antibody. Furthermore, unlike normal T cells, they failed to respond to the antibody even when phorbol ester was added. The addition of supplementary cytokines did not correct this defect. These studies indicate that MRL/lpr DNT constitutively and aberrantly express VEA but do not respond when it is cross-linked. These abnormalities may result from the failure to express Fas, the recently reported apoptosis-inducing receptor defective in lpr mice.
MRL/Mp-lpr/lpr（MRL/lpr）小鼠会出现明显的淋巴结病，主要特征是Thy1+CD3+CD4-CD8-细胞（“双阴性T细胞”；DNT）。矛盾的是，当通过CD3或丝裂原刺激时，DNT在体外增殖能力很差。针对树突状表皮DNT产生的仓鼠单克隆抗体H1.2F3识别一种非常早期的激活（VEA）抗原，静止细胞通常不表达该抗原，但在用刀豆蛋白A或佛波酯激活T细胞后很快就会表达。在抗原呈递细胞（APC）和佛波酯存在的情况下，这种二硫键连接的二聚体的交联会诱导正常T细胞增殖。因此，我们测试了MRL/lpr DNT是否表达这种抗原，以及它是否可能在DNT扩增中起作用。来自肿大的MRL/lpr淋巴结的未处理细胞以年龄依赖性方式表达VEA，在3至4月龄时达到峰值。在同基因MRL/Mp(-)+/+品系的一小部分淋巴细胞中仅观察到有限的表达。新鲜收获的MRL/lpr淋巴细胞上的VEA表达主要见于DNT，但对DNT进行VEA抗原和已知存在于lpr DNT上的其他三种标志物的双重染色显示，DNT是一个异质性群体。此外，一些CD4+T细胞表达VEA抗原。尽管MRL/lpr DNT组成性地表达VEA抗原，但它们对与H1.2F3抗体交联没有增殖反应。此外，与正常T细胞不同，即使添加了佛波酯，它们也对该抗体无反应。添加补充细胞因子并不能纠正这一缺陷。这些研究表明，MRL/lpr DNT组成性且异常地表达VEA，但在其交联时无反应。这些异常可能是由于未能表达Fas所致，Fas是最近报道的lpr小鼠中缺陷的凋亡诱导受体。
