This study identifies a novel non-ELR CXC chemokine, I-TAC (interferon-inducible T cell alpha chemoattractant), through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. I-TAC is regulated by interferons (IFNs) and has potent chemoattractant activity for interleukin (IL)-2-activated T cells, but not for unstimulated T cells, neutrophils, or monocytes. I-TAC selectively interacts with CXCR3, the receptor for two other IFN-inducible chemokines, IP-10 and HuMig, with a significantly higher affinity. I-TAC demonstrates higher potency and efficacy than IP-10 and HuMig in mobilizing intracellular calcium and inducing chemotaxis in activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-γ and IL-1 results in a ~400,000-fold increase in I-TAC mRNA expression, suggesting that I-TAC could be a major chemoattractant for effector T cells involved in neuroinflammatory disorders. The high expression of I-TAC in IFN- and IL-1-stimulated astrocytes indicates its potential role in recruiting effector T cells during immune responses dominated by IFNs.This study identifies a novel non-ELR CXC chemokine, I-TAC (interferon-inducible T cell alpha chemoattractant), through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. I-TAC is regulated by interferons (IFNs) and has potent chemoattractant activity for interleukin (IL)-2-activated T cells, but not for unstimulated T cells, neutrophils, or monocytes. I-TAC selectively interacts with CXCR3, the receptor for two other IFN-inducible chemokines, IP-10 and HuMig, with a significantly higher affinity. I-TAC demonstrates higher potency and efficacy than IP-10 and HuMig in mobilizing intracellular calcium and inducing chemotaxis in activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-γ and IL-1 results in a ~400,000-fold increase in I-TAC mRNA expression, suggesting that I-TAC could be a major chemoattractant for effector T cells involved in neuroinflammatory disorders. The high expression of I-TAC in IFN- and IL-1-stimulated astrocytes indicates its potential role in recruiting effector T cells during immune responses dominated by IFNs.