Harding C V, Pfeifer J D
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Immunology. 1994 Dec;83(4):670-4.
Macrophages were shown to mediate class I major histocompatibility complex (MHC-1) presentation of a fusion protein (Crl-OVA) expressed in Salmonella typhimurium, a bacterium which fails to escape from vacuolar compartments after phagocytosis or penetration into host cells. Salmonella typhimurium also penetrates into non-phagocytic intestinal epithelial cells, a portal of entry for systemic infection. We tested the ability of infected epithelial cells to process antigen expressed by S. typhimurium for presentation by MHC-I molecules to CD8+ T cells. CMT-93 murine adenocarcinoma cells expressed Kb and effectively presented the OVA 257-264 peptide to CD8 OVA T-hybridoma cells, but infected CMT-93 cells failed to process Crl-OVA expressed in S. typhimurium. Therapeutically useful MHC-I-restricted cytotoxic T-lymphocyte (CTL) responses may be generated by macrophage presentation of Salmonella antigens or recombinant antigens expressed in Salmonella vaccine vectors. Our data suggest that an inability of epithelial cells to present these antigens may limit the utility of CTL in epithelial immunity in salmonellosis, but studies of additional epithelial cell systems are needed.
巨噬细胞被证明可介导鼠伤寒沙门氏菌中表达的融合蛋白(Crl-OVA)的I类主要组织相容性复合体(MHC-1)呈递,鼠伤寒沙门氏菌在吞噬作用或侵入宿主细胞后无法从液泡区室逃逸。鼠伤寒沙门氏菌还可侵入非吞噬性肠上皮细胞,这是全身感染的一个入口。我们测试了受感染上皮细胞处理鼠伤寒沙门氏菌表达的抗原并通过MHC-I分子呈递给CD8+T细胞的能力。CMT-93鼠腺癌细胞表达Kb,并有效地将OVA 257-264肽呈递给CD8 OVA T杂交瘤细胞,但受感染的CMT-93细胞无法处理鼠伤寒沙门氏菌中表达的Crl-OVA。巨噬细胞呈递沙门氏菌抗原或沙门氏菌疫苗载体中表达的重组抗原可能会产生具有治疗作用的MHC-I限制性细胞毒性T淋巴细胞(CTL)反应。我们的数据表明,上皮细胞无法呈递这些抗原可能会限制CTL在沙门氏菌病上皮免疫中的效用,但还需要对其他上皮细胞系统进行研究。