Sakai T, Agui T, Matsumoto K
Institute for Animal Experimentation, University of Tokushima School of Medicine, Japan.
Cell Immunol. 1994 Oct 15;158(2):414-22. doi: 10.1006/cimm.1994.1287.
LEC rats show a congenital maturational arrest from CD4+8+ to CD4+8- but not to CD4-8+ cells in the thymus. However, some CD4+ cells exist in peripheral lymph nodes. In normal F344 rats, a part of CD4+ T cells expressed CD8 molecules upon concanavaline A (Con A) stimulation. The percentage of CD4+8+ cells and the level of CD8 expression in F344 rat CD4+ cells were enhanced by the glucocorticoid hormone dexamethasone. In contrast, although LEC rat CD4+ cells induced DNA synthesis normally upon Con A stimulation, expression of CD8 was significantly reduced. Furthermore, addition of dexamethasone did not restore the inhibition of CD8 expression. However, LEC rat CD4+ cells could induce CD8 expression, when stimulated by T cell receptor (TCR) cross-linking with anti-TCR monoclonal antibody, suggesting that the TCR-mediated signal is normally transduced in LEC rat CD4+ cells. On the other hand, LEC rat CD4+ cells showed normal expression of major histocompatibility complex (MHC) class II antigens, when stimulated by either Con A or TCR cross-linking, indicating that signals for the induction of MHC class II expression are normal in LEC rat CD4+ cells. Activation of peripheral CD4+ cells has been reported to induce simultaneous expression of CD8 and MHC class II molecules in rats. However, our results using LEC rat CD4+ cells suggest that Con A-induced signaling pathways for CD8 and MHC class II expression can be separable.
LEC大鼠在胸腺中表现出从CD4⁺8⁺到CD4⁺8⁻细胞的先天性成熟停滞,但不会停滞到CD4⁻8⁺细胞。然而,外周淋巴结中存在一些CD4⁺细胞。在正常的F344大鼠中,一部分CD4⁺T细胞在刀豆球蛋白A(Con A)刺激下表达CD8分子。糖皮质激素地塞米松可提高F344大鼠CD4⁺细胞中CD4⁺8⁺细胞的百分比和CD8表达水平。相比之下,尽管LEC大鼠CD4⁺细胞在Con A刺激下能正常诱导DNA合成,但CD8的表达显著降低。此外,添加地塞米松并不能恢复对CD8表达的抑制。然而,当用抗TCR单克隆抗体交联T细胞受体(TCR)刺激时,LEC大鼠CD4⁺细胞可诱导CD8表达,这表明TCR介导的信号在LEC大鼠CD4⁺细胞中正常转导。另一方面,当用Con A或TCR交联刺激时,LEC大鼠CD4⁺细胞主要组织相容性复合体(MHC)II类抗原表达正常,这表明LEC大鼠CD4⁺细胞中诱导MHC II类表达的信号正常。据报道,大鼠外周CD4⁺细胞的激活可诱导CD8和MHC II类分子同时表达。然而,我们使用LEC大鼠CD4⁺细胞的结果表明,Con A诱导的CD8和MHC II类表达的信号通路可能是可分离的。