Requirement of the IFN‐α/β‐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‐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 CD44 low 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.