Beatty P R, Stephens R S
Program in Infectious Diseases, University of California at Berkeley 94720.
J Immunol. 1994 Nov 15;153(10):4588-95.
Intracellular bacterial pathogens have evolved to either grow in the nutrient-rich cytoplasm or remain sequestered within a vacuole. One potentially important selective advantage for growth within a vacuole may be evasion of cell-mediated detection and cytolysis. To address this question we used the endosomally confined bacterium Chlamydia trachomatis, which naturally infects epithelial cells, to examine CTL-mediated lysis of nonphagocytic cells. CTL-mediated lysis of infected target cells was detected, although the increased expression of ICAM-1 by transfection was required. The elimination of CD8+ T cells or addition of brefeldin A or cycloheximide eliminated specific cytolysis, whereas conversely, treatment with chloroquine or ammonium chloride had only minor effects. These results implicate endogenous Ag processing for Chlamydia-specific cytolysis. This work demonstrates CTL-mediated lysis of cells infected with an intracellular bacterium that inhibits lysosomal fusion and is confined to an endosomal vacuole.
细胞内细菌病原体已经进化到要么在营养丰富的细胞质中生长,要么被隔离在液泡内。在液泡内生长的一个潜在重要的选择优势可能是逃避细胞介导的检测和细胞溶解。为了解决这个问题,我们使用了自然感染上皮细胞的、被内体限制的细菌沙眼衣原体,来检测细胞毒性T淋巴细胞(CTL)介导的非吞噬细胞的溶解。尽管需要通过转染增加细胞间黏附分子-1(ICAM-1)的表达,但仍检测到CTL介导的感染靶细胞的溶解。消除CD8 + T细胞或添加布雷菲德菌素A或环己酰亚胺可消除特异性细胞溶解,而相反,用氯喹或氯化铵处理只有轻微影响。这些结果表明内源性抗原加工参与了沙眼衣原体特异性细胞溶解。这项工作证明了CTL介导的对感染了抑制溶酶体融合并局限于内体液泡的细胞内细菌的细胞溶解作用。