Berg M, Murakawa Y, Camerini D, James S P
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Gastroenterology. 1991 Jul;101(1):90-9. doi: 10.1016/0016-5085(91)90464-v.
The Leu-8 membrane glycoprotein is the primate homologue of the murine MEL-14 peripheral lymph node homing receptor and is expressed on a majority of circulating lymphocytes but on few lymphocytes in the intestinal lamina propria. To examine the mechanisms regulating expression of the Leu-8-molecule on lymphocytes in different tissue sites, studies of Leu-8 membrane antigen expression, Leu-8 messenger RNA, and the Leu-8 gene were performed using normal human and nonhuman primate lymphocytes. Activation of resting peripheral blood lymphocytes caused a rapid decrease in membrane Leu-8 expression, a more gradual decrease in Leu-8 messenger RNA, and an increase in expression of interleukin 2 and interleukin 2 receptor messenger RNA. However, the down regulation of Leu-8 expression during activation was reversible because both membrane Leu-8 antigen and Leu-8 messenger RNA were reexpressed after 5 days of culture. Leu-8 messenger RNA was present in lymphocytes isolated from peripheral blood, spleen, and, particularly, mesenteric lymph node, but intestinal lamina propria lymphocytes contained very low levels of Leu-8 messenger RNA. The absence of Leu-8 messenger RNA in intestinal lymphocytes and circulating Leu-8 negative lymphocytes was not caused by recent activation in vivo because these cells did not have detectable interleukin 2 messenger RNA, and intestinal lymphocytes did not express Leu-8 after culture in vitro. Phorbol myristate acetate was found to be a strong inducer of Leu-8 messenger RNA in Leu-8-positive lymphocytes; however, phorbol myristate acetate did not induce membrane Leu-8 expression or Leu-8 messenger RNA in lamina propria lymphocytes. Leu-8-negative lymphocytes in peripheral blood or lamina propria did not have evidence of deletion or rearrangement of the Leu-8 gene. Leu-8-positive Jurkat cells and peripheral blood lymphocytes and Leu-8-negative peripheral blood and intestinal lymphocytes had partial methylation of an Msp I site in proximity to the Leu-8 gene, suggesting that in Leu-8-negative lymphocytes, the Leu-8 gene previously was transcriptionally active. In summary, these studies demonstrate that intestinal lamina propria lymphocytes have the same characteristics as circulating Leu-8-negative lymphocytes with respect to their state of activation and inability to express the Leu-8 antigen. The results suggest that the majority of lymphocytes that migrate to the intestinal lamina propria are derived from the subpopulation of circulating Leu-8-negative lymphocytes.
亮氨酸-8膜糖蛋白是小鼠MEL-14外周淋巴结归巢受体的灵长类同源物，在大多数循环淋巴细胞上表达，但在肠固有层的淋巴细胞上很少表达。为了研究不同组织部位淋巴细胞上亮氨酸-8分子表达的调控机制，使用正常人和非人灵长类淋巴细胞进行了亮氨酸-8膜抗原表达、亮氨酸-8信使核糖核酸及亮氨酸-8基因的研究。静息外周血淋巴细胞的激活导致膜亮氨酸-8表达迅速下降，亮氨酸-8信使核糖核酸逐渐减少，白细胞介素2及白细胞介素2受体信使核糖核酸表达增加。然而，激活过程中亮氨酸-8表达的下调是可逆的，因为培养5天后膜亮氨酸-8抗原和亮氨酸-8信使核糖核酸都重新表达。亮氨酸-8信使核糖核酸存在于从外周血、脾脏尤其是肠系膜淋巴结分离的淋巴细胞中，但肠固有层淋巴细胞中亮氨酸-8信使核糖核酸水平极低。肠淋巴细胞和循环中亮氨酸-8阴性淋巴细胞中亮氨酸-8信使核糖核酸的缺失并非由体内近期激活所致，因为这些细胞检测不到白细胞介素2信使核糖核酸，且肠淋巴细胞在体外培养后也不表达亮氨酸-8。佛波醇肉豆蔻酸酯被发现是亮氨酸-8阳性淋巴细胞中亮氨酸-8信使核糖核酸的强诱导剂；然而，佛波醇肉豆蔻酸酯在固有层淋巴细胞中不诱导膜亮氨酸-8表达或亮氨酸-8信使核糖核酸。外周血或固有层中亮氨酸-8阴性淋巴细胞没有亮氨酸-8基因缺失或重排的证据。亮氨酸-8阳性的Jurkat细胞、外周血淋巴细胞以及亮氨酸-8阴性的外周血和肠淋巴细胞在亮氨酸-8基因附近的一个Msp I位点有部分甲基化，这表明在亮氨酸-8阴性淋巴细胞中，亮氨酸-8基因以前是转录活跃的。总之，这些研究表明，肠固有层淋巴细胞在激活状态和无法表达亮氨酸-8抗原方面与循环中亮氨酸-8阴性淋巴细胞具有相同特征。结果提示，迁移至肠固有层的大多数淋巴细胞来源于循环中亮氨酸-8阴性淋巴细胞亚群。
