Geginat G, Nichterlein T, Kretschmar M, Schenk S, Hof H, Lalic-Mülthaler M, Goebel W, Bubert A
Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
J Immunol. 1999 Apr 15;162(8):4781-9.
The contact of T cells to cross-reactive antigenic determinants expressed by nonpathogenic environmental micro-organisms may contribute to the induction or maintenance of T cell memory. This hypothesis was evaluated in the model of murine Listeria monocytogenes infection. The influence of nonpathogenic L. innocua on the L. monocytogenes p60-specific T cell response was analyzed. We show that some CD4 T cell clones raised against purified p60 from L. monocytogenes cross-react with p60 purified from L. innocua. The L. monocytogenes p60-specific CD4 T cell clone 1A recognized the corresponding L. innocua p60 peptide QAAKPAPAPSTN, which differs only in the first amino acid residue. In vitro experiments revealed that after L. monocytogenes infection of APCs, MHC class I-restricted presentation of p60 occurs, while MHC class II-restricted p60 presentation is inhibited. L. innocua-infected cells presented p60 more weakly but equally well in the context of both MHC class I and MHC class II. In contrast to these in vitro experiments the infection of mice with L. monocytogenes induced a strong p60-specific CD4 and CD8 T cell response, while L. innocua infection failed to induce p60-specific T cells. L. innocua booster infection, however, expanded p60-specific memory T cells induced by previous L. monocytogenes infection. In conclusion, these findings suggest that infection with a frequently occurring environmental bacterium such as L. innocua, which is nonpathogenic and not adapted to intracellular replication, can contribute to the maintenance of memory T cells specific for a related intracellular pathogen.
T细胞与非致病性环境微生物所表达的交叉反应性抗原决定簇的接触，可能有助于T细胞记忆的诱导或维持。该假说在小鼠单核细胞增生李斯特菌感染模型中得到了评估。分析了无害李斯特菌对单核细胞增生李斯特菌p60特异性T细胞反应的影响。我们发现，一些针对单核细胞增生李斯特菌纯化p60产生的CD4 T细胞克隆与从无害李斯特菌纯化的p60发生交叉反应。单核细胞增生李斯特菌p60特异性CD4 T细胞克隆1A识别相应的无害李斯特菌p60肽QAAKPAPAPSTN，两者仅在第一个氨基酸残基上有所不同。体外实验表明，在单核细胞增生李斯特菌感染抗原呈递细胞（APC）后，会发生MHC I类限制性的p60呈递，而MHC II类限制性的p60呈递则受到抑制。无害李斯特菌感染的细胞呈递p60的能力较弱，但在MHC I类和MHC II类背景下呈递效果相同。与这些体外实验不同的是，用单核细胞增生李斯特菌感染小鼠会诱导强烈的p60特异性CD4和CD8 T细胞反应，而无害李斯特菌感染则未能诱导p60特异性T细胞。然而，无害李斯特菌加强感染会使先前单核细胞增生李斯特菌感染诱导产生的p60特异性记忆T细胞扩增。总之，这些发现表明，感染一种常见的环境细菌，如无害李斯特菌，这种细菌无致病性且不适应细胞内复制，可有助于维持针对相关细胞内病原体的记忆T细胞。
