Mata M, Paterson Y
Department of Microbiology, University of Pennsylvania Medical School, Philadelphia 19104, USA.
J Immunol. 1999 Aug 1;163(3):1449-56.
Listeria monocytogenes is a facultative intracellular bacterium that lives and grows in the cytoplasm of the host cell. The hallmark of a listerial infection is a cell-mediated immune response to its own secreted virulence factors. Thus, L. monocytogenes vaccines engineered to secrete HIV proteins may be ideal vectors for boosting cellular immune responses against HIV. Using strains of L. monocytogenes that stably express and secrete HIV Gag (Lm-Gag) to deliver this Ag to the immune system, we have previously shown strong MHC class I-restricted cytotoxic T cell responses to this protein. In this study, we examine MHC class II-restricted T cell responses to HIV-Gag delivered by Lm-Gag. We demonstrate the induction of CD4+ T cells that are HIV-Gag specific and identify three epitopes in two strains of mice, BALB/c (H-2d) and C57BL/6 (H-2b), two of which are both H-2d and H-2b restricted, but are not immunodominant for both haplotypes. In addition, we show that the CD4+ T cells induced are of the Th1 phenotype that produce IFN-gamma at levels similar to CD4+ T cells induced to endogenous listerial Ags. These studies suggest that chromosomally modified strains of L. monocytogenes may be useful as vaccine vectors for the induction of Th1 T cell responses against HIV.
单核细胞增生李斯特菌是一种兼性胞内细菌，在宿主细胞的细胞质中生存和生长。李斯特菌感染的标志是针对其自身分泌的毒力因子的细胞介导免疫反应。因此，经基因工程改造以分泌HIV蛋白的单核细胞增生李斯特菌疫苗可能是增强针对HIV的细胞免疫反应的理想载体。利用稳定表达并分泌HIV Gag（Lm-Gag）的单核细胞增生李斯特菌菌株将该抗原递送至免疫系统，我们先前已证明针对该蛋白有强烈的MHC I类限制性细胞毒性T细胞反应。在本研究中，我们检测了Lm-Gag递送的HIV-Gag的MHC II类限制性T细胞反应。我们证明了诱导出了HIV-Gag特异性的CD4 + T细胞，并在两种小鼠品系BALB/c（H-2d）和C57BL/6（H-2b）中鉴定出三个表位，其中两个表位同时受H-2d和H-2b限制，但并非对两种单倍型均具有免疫优势。此外，我们表明诱导出的CD4 + T细胞具有Th1表型，产生的IFN-γ水平与针对内源性李斯特菌抗原诱导出的CD4 + T细胞相似。这些研究表明，经染色体修饰的单核细胞增生李斯特菌菌株可能作为诱导针对HIV的Th1 T细胞反应的疫苗载体。
