Kadena T, Matsuzaki G, Fujise S, Kishihara K, Takimoto H, Sasaki M, Beppu M, Nakamura S, Nomoto K
Department of Immunology, Kyushu University, Japan.
Immunology. 1997 Aug;91(4):511-9. doi: 10.1046/j.1365-2567.1997.00303.x.
T-cell receptor (TCR) alpha beta+ CD4- CD8- (double-negative; DN) T cells appear in the peritoneal cavity at an early stage of intraperitoneal (i.p.) infection with the intracellular pathogen Listeria monocytogenes. In the present report, we analysed the developmental pathway and functions of the TCR alpha beta+ DN T cells using the L. monocytogenes infection system. The TCR alpha beta+ DN T cells appeared in the peritoneal cavity after L. monocytogenes i.p. infection in adult-thymectomized lethally irradiated bone marrow chimeras and p56lck-deficient mice. The results demonstrated that the TCR alpha beta+ DN T cells can develop extrathymically in a p56lck-independent manner. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the TCR alpha beta+ DN T cells expressed genes for interferon-gamma (IFN-gamma), the macrophage chemotactic factors MCP-1 and Eta-1, and granulocyte-macrophage colony-stimulating factor (GM-CSF) but lacked expression of genes for interleukin-2 (IL-2), IL-4 and IL-10. As expected from the RT-PCR analysis, the TCR alpha beta+ DN T cells produced IFN-gamma in response to anti-TCR beta monoclonal antibody (mAb), anti-CD3 mAb and L. monocytogenes-infected macrophages but IL-4 was undetectable after the stimulation. Furthermore, the intracellular cytokine staining analysis demonstrated that approximately half of the TCR alpha beta+ DN T cells detectable at the early stage of L. monocytogenes infection were IFN-gamma-producing cells. All of the results suggest that the TCR alpha beta+ DN T cells develop through a unique extrathymic p56lck-independent pathway and participate in early protection against bacterial infection through activation and accumulation of macrophages.
T细胞受体(TCR)αβ⁺ CD4⁻ CD8⁻(双阴性;DN)T细胞在细胞内病原体单核细胞增生李斯特菌腹腔内(i.p.)感染的早期出现在腹腔中。在本报告中,我们使用单核细胞增生李斯特菌感染系统分析了TCRαβ⁺ DN T细胞的发育途径和功能。TCRαβ⁺ DN T细胞在成年胸腺切除的致死性照射骨髓嵌合体和p56lck缺陷小鼠腹腔内感染单核细胞增生李斯特菌后出现在腹腔中。结果表明,TCRαβ⁺ DN T细胞可以以不依赖p56lck的方式在胸腺外发育。逆转录-聚合酶链反应(RT-PCR)分析表明,TCRαβ⁺ DN T细胞表达干扰素-γ(IFN-γ)、巨噬细胞趋化因子MCP-1和Eta-1以及粒细胞-巨噬细胞集落刺激因子(GM-CSF)的基因,但缺乏白细胞介素-2(IL-2)、IL-4和IL-10的基因表达。正如RT-PCR分析所预期的那样,TCRαβ⁺ DN T细胞在抗TCRβ单克隆抗体(mAb)、抗CD3 mAb和单核细胞增生李斯特菌感染的巨噬细胞刺激下产生IFN-γ,但刺激后未检测到IL-4。此外,细胞内细胞因子染色分析表明,在单核细胞增生李斯特菌感染早期可检测到的TCRαβ⁺ DN T细胞中,约一半是产生IFN-γ的细胞。所有结果表明,TCRαβ⁺ DN T细胞通过独特的胸腺外p56lck非依赖途径发育,并通过巨噬细胞的激活和聚集参与对细菌感染的早期保护。