TCR αβ+ CD4− CD8− T cells differentiate extrathymically in an lck‐independent manner and participate in early response against Listeria monocytogenes infection through interferon‐γ production
TCR αβ+ CD4− CD8− T cells differentiate extrathymically in an lck‐independent manner and participate in early response against Listeria monocytogenes infection through interferon‐γ production
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TCR αβ+ CD4− CD8− T 细胞以不依赖 lck 的方式在胸腺外分化，并通过产生干扰素 γ 参与针对单核细胞增生李斯特菌感染的早期反应
DOI：
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
K. Nomoto
中科院分区：
文献类型：
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作者：
T. Kadena;Goro Matsuzaki;S. Fujise;K. Kishihara;Hiroaki Takimoto;M. Sasaki;M. Beppu;Seiji Nakamura;K. Nomoto
T细胞受体(Tcr)αβ+CD4−CD8−(双阴性；DN)T 细胞在腹膜腔早期出现。感染细胞内病原体单核细胞增多性李斯特菌。在本报告中，我们利用单核细胞增多性乳杆菌感染系统分析了TCRαβ+dN T 细胞的发育途径和功能。腹腔注射单核细胞增多性乳杆菌后，出现Tcrαβ+dN T 细胞。成年胸腺切除致死性照射骨髓嵌合体和p56lck缺陷小鼠的感染。结果表明，TCRαβ+dN T 细胞能以p56lck非依赖性方式在胸腺外发育。逆转录-聚合酶链式反应分析显示，TCRαβ+DN T 细胞表达干扰素-γ、巨噬细胞趋化因子MCP-1和ETA-1、粒细胞-巨噬细胞集落刺激因子基因，但不表达IL-2、IL-4和IL-10基因。正如RT-γ分析所预期的那样，TCRαβ+DN T 细胞产生干扰素-γ与抗TCRβ单抗反应。抗CD3- 单抗和单核细胞增多性李斯特氏菌感染巨噬细胞，刺激后未检测到IL-4。此外，细胞内细胞因子染色分析表明，在单核细胞增多性李氏杆菌感染早期可检测到的TCRαβ+dN T 细胞中，约有一半是产生干扰素-γ的细胞。以上结果提示，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积聚参与细菌感染的早期保护。
T‐cell receptor (TCR) αβ+ 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 TCRαβ+ DN T cells using the L. monocytogenes infection system. The TCRαβ+ 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 TCRαβ+ DN T cells can develop extrathymically in a p56lck‐independent manner. Reverse transcription–polymerase chain reaction (RT‐PCR) analysis showed that the TCRαβ+ DN T cells expressed genes for interferon‐γ (IFN‐γ), 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 TCRαβ+ DN T cells produced IFN‐γ in response to anti‐TCRβ 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 TCRαβ+ DN T cells detectable at the early stage of L. monocytogenes infection were IFN‐γ‐producing cells. All of the results suggest that the TCRαβ+ 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.