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 p56(lck)-deficient mice. The results demonstrated that the TCRαβ+ DN T cells can develop extrathymically in a p56(lck)-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 p56(lck)-independent pathway and participate in early protection against bacterial infection through activation and accumulation of macrophages.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy