Requirement of the IFN‐α/β‐induced CXCR3 chemokine signalling for CD8+ T cell activation

• DOI: 10.1046/j.1365-2443.2002.00515.x
• Publication Date: 2003-03-11T22:49:07Z
• Authors: Kouetsu Ogasawara; Shigeaki Hida; Youmin Weng; Akio Saiura; Kojiro Sato; Hiroshi Takayanagi; Shinya Sakaguchi; Taeko Yokochi; Tatsuhiko Kodama; Makoto Naitoh; Julie A. De Martino; Tadatsugu Taniguchi
• Keywords: Receptors, CXCR3; Receptors, Antigen, T-Cell; Interferon-alpha; CD8-Positive T-Lymphocytes; Lymphocyte Activation; Recombinant Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Interferon Type I; Animals; Receptors, Chemokine; Cells, Cultured; Signal Transduction

AbstractBackground: Activation of both CD4+ T and CD8+ T cells is triggered by the engagement of the T cell antigen receptor (TCR) with MHC/peptide complexes on antigen‐presenting cells. This process also requires other molecular interactions, which transmit co‐stimulatory signals to these T cells. To ensure an effective immune response, distinct T cell subsets may additionally employ unique mechanism(s) for efficient activation.Results: We here show that mutant CD8+ T cells lacking the IFN‐α/β signalling components are hyporesponsive to antigen stimulation in vitro. We further show that IFN‐α/β‐mediated signals are required for induction of the chemokines IP‐10/I‐TAC and their common receptor, CXCR3, and in turn provide evidence that CXCR3‐mediated signals indeed function in the activation and proliferation of CD8+ T cells, particularly for the CD44low naive phenotype cells.Conclusion: The CXCR3 chemokine system is regulated by IFN‐α/β in CD8+ T cells, and it is critical for the efficient cell activation. The present study therefore reveals a novel role of the IFN‐α/β–CXCR3 signalling cascade in CD8+ T cell activation.