Requirement of the IFN-alpha/beta-induced CXCR3 chemokine signalling for CD8+ T cell activation

BACKGROUND: 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-alpha/beta signalling components are hyporesponsive to antigen stimulation in vitro. We further show that IFN-alpha/beta-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-alpha/beta in CD8+ T cells, and it is critical for the efficient cell activation. The present study therefore reveals a novel role of the IFN-alpha/beta-CXCR3 signalling cascade in CD8+ T cell activation.