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Expression of IFN-Inducible T Cell Chemoattractant by Human Endothelial Cells Is Cyclosporin A-Resistant and Promotes T Cell Adhesion: Implications for Cyclosporin A-Resistant Immune Inflammation¹

Melissa M. Mazanet^*, Kuldeep Neote and Christopher C. W. Hughes^2,*

^* Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and Department of Molecular Sciences, Pfizer Inc., Groton, CT 06340

IFN-inducible T cell chemoattractant (I-TAC) is a recently discovered member of the CXC chemokine family. It is a potent T cell chemoattractant expressed by IFN--treated astrocytes, monocytes, keratinocytes, bronchial epithelial cells, and neutrophils. In this study, we show that I-TAC is also expressed by IFN--treated endothelial cells (EC), both at the mRNA and protein levels. Induction of the I-TAC message is rapid and sustained over 24 h. TNF- does not induce I-TAC mRNA alone, but does act synergistically with IFN-. Blocking Abs to I-TAC, or to its receptor, CXCR3, reduce T cell adhesion to EC monolayers demonstrating that the expressed protein is functional. Finally, the expression of I-TAC by EC is resistant to the immunosuppressive drug cyclosporin A, suggesting that I-TAC may contribute to the chronic immune inflammation characteristic of graft arteriosclerosis.

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