Falgarone G, Blanchard H S, Virecoulon F, Simonet M, Breban M
Institut National de la Santé et de la Recherche Médicale, Unit 477, Institut de Rhumatologie, Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Université René Descartes, Paris, France.
J Immunol. 1999 Mar 1;162(5):2875-83.
Yersinia pseudotuberculosis is a pathogenic enteric bacteria that evades host cellular immune response and resides extracellularly in vivo. Nevertheless, an important contribution of T cells to defense against Yersinia has been previously established. In this study we demonstrate that Lewis rats infected with virulent strains of Y. pseudotuberculosis, mount a Yersinia-specific, RT1-A-restricted, CD8+ T cell-mediated, cytotoxic response. Sensitization of lymphoblast target cells for cytolysis by Yersinia-specific CTLs required their incubation with live Yersinia and was independent of endocytosis. Although fully virulent Yersinia did not invade those cells, they attached to their surface. In contrast, invasin-deficient strain failed to bind to blast targets or to sensitize them for cytolysis. Furthermore, an intact virulence plasmid was an absolute requirement for Yersinia to sensitize blast targets for cytolysis. Using a series of Y. pseudotuberculosis mutants selectively deficient in virulence plasmid-encoded proteins, we found no evidence for a specific role played by YadA, YopH, YpkA, or YopJ in the sensitization process of blast targets. In contrast, mutations suppressing YopB, YopD, or YopE expression abolished the capacity of Yersinia to sensitize blast targets. These results are consistent with a model in which extracellular Yersinia bound to lymphoblast targets via invasin translocate inside eukaryotic cytosol YopE, which is presented in a class I-restricted fashion to CD8+ cytotoxic T cells. This system could represent a more general mechanism by which bacteria harboring a host cell contact-dependent or type III secretion apparatus trigger a class I-restricted CD8+ T cell response.
假结核耶尔森菌是一种致病性肠道细菌，它能逃避宿主细胞免疫反应并在体内细胞外生存。然而，此前已证实T细胞在抵御耶尔森菌方面发挥着重要作用。在本研究中，我们证明感染了强毒株假结核耶尔森菌的刘易斯大鼠会产生一种针对耶尔森菌的、受RT1 - A限制的、由CD8 + T细胞介导的细胞毒性反应。用耶尔森菌特异性CTL使淋巴母细胞靶细胞对细胞溶解敏感，需要将它们与活的耶尔森菌一起孵育，且与内吞作用无关。尽管完全有毒力的耶尔森菌不会侵入这些细胞，但它们会附着在细胞表面。相比之下，缺乏侵袭素的菌株无法与母细胞靶标结合或使其对细胞溶解敏感。此外，完整的毒力质粒是耶尔森菌使母细胞靶标对细胞溶解敏感的绝对必要条件。使用一系列选择性缺乏毒力质粒编码蛋白的假结核耶尔森菌突变体，我们没有发现YadA、YopH、YpkA或YopJ在母细胞靶标致敏过程中发挥特定作用的证据。相反，抑制YopB、YopD或YopE表达的突变消除了耶尔森菌使母细胞靶标致敏的能力。这些结果与一个模型一致，即细胞外的耶尔森菌通过侵袭素与淋巴母细胞靶标结合，将YopE转运到真核细胞胞质溶胶中，以I类限制的方式呈递给CD8 + 细胞毒性T细胞。这个系统可能代表了一种更普遍的机制，通过这种机制，具有宿主细胞接触依赖性或III型分泌装置的细菌触发I类限制的CD8 + T细胞反应。
