HUMAN INTESTINAL EPITHELIAL CELL-INDUCED CD8(+) T-CELL ACTIVATION IS MEDIATED THROUGH CD8 AND THE ACTIVATION OF CD8-ASSOCIATED P56(LCK)
HUMAN INTESTINAL EPITHELIAL CELL-INDUCED CD8(+) T-CELL ACTIVATION IS MEDIATED THROUGH CD8 AND THE ACTIVATION OF CD8-ASSOCIATED P56(LCK)
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DOI：
10.1084/jem.182.4.1079
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发表时间：
1995-10-01
影响因子：
15.3
通讯作者：
MAYER, L
中科院分区：
文献类型：
--
作者：
LI, Y;YIO, XY;MAYER, L
抗原特异性或同种异体混合细胞中正常肠上皮细胞对CD8(+)抑制性T细胞的激活培养系统对粘膜免疫反应的调节有重要意义。在这项研究中，我们发现上皮细胞诱导CD8(+)抑制性T细胞激活的能力似乎与T细胞表面CD8分子的结合有关。这似乎是由上皮细胞表面表达的非I类分子介导的，该分子与CD8结合，并导致CD8相关的src样酪氨酸激酶p56(Lck)的激活。上皮细胞刺激的p56(Lck)激活是一个早期事件(与单核细胞相反)，对T细胞的激活是必不可少的，因为用蛋白酪氨酸激酶抑制剂genstein或herbamcin可以完全抑制T细胞的增殖。T细胞用抗CD8抗体或肠上皮细胞用抗上皮细胞单抗B9预处理可抑制p56(Lck)的激活，并进一步证实T细胞上的CD8和上皮细胞上的CD8配体参与了这一T细胞激活事件。用分别表达CD_4和CD_8的3G4和3G8转基因小鼠的实验证实了该反应的特异性。3G8与上皮细胞共培养，但不与单核细胞共培养，激活p56(Lck)，而以单核细胞为刺激细胞时，3G4细胞优先激活p56(Lck)。尽管CD8和CD8相关的p56(Lck)的刺激对于上皮细胞诱导的T细胞活化是重要的，但单用CD8和抗CD8的单抗不能单独诱导T细胞的增殖。这些数据表明，上皮细胞驱动的T细胞增殖还需要第二个信号，可能是通过T细胞抗原受体，因为T细胞受体相关的激酶Fyn也被激活了。
The activation of CD8(+) suppressor T cells by normal intestinal epithelial cells in antigen-specific or allogeneic mixed cell. culture systems has significant implications for the regulation of mucosal immune responses. In this study, we found that the capacity of epithelial cells to induce CD8(+) suppressor T cell activation appeared to be linked to the binding of CD8 molecules on the T cell surface. This appears to be mediated by a non-class I molecule expressed on the epithelial cell surface, which binds to CD8 and results in the activation of the CD8-associated src-like tyrosine kinase, p56(lck). Epithelial cell-stimulated p56(lck) activation is an early event (in contrast to monocytes) and is essential for T cell activation, since proliferation could be completely abrogated by pretreatment of T cells with genestein or herbamycin, both of which are protein tyrosine kinase inhibitors. Pretreatment of T cells with anti-CD8 or of intestinal epithelial cells with an anti-epithelial cell mAb B9 inhibited p56(lck) activation and further confirmed that CD8 on the T cell and a CD8 ligand on the epithelial cell were involved in this T cell activation event. The specificity of this reaction was confirmed in experiments in which murine transfectants 3G4 and 3G8, expressing CD4 or CD8, respectively, were used. Coculture of 3G8 with epithelial cells but not with monocytes activated p56(lck) in this cell line, whereas p56(lck) was preferentially activated in 3G4 cells when monocytes were used as the stimulator cells. Although stimulation through CD8- and CD8-associated p56(lck) was important for epithelial cell-induced T cell activation, T cell proliferation could not be induced by crosslinking CD8 alone with monoclonal antibody anti-CD8. These data suggest that a second signal, possibly through the T cell antigen receptor since activation of the T cell receptor-associated kinase fyn was also seen, is required for epithelial cell-driven T cell proliferation.