Differential expression of three T lymphocyte-activating CXC chemokines byhuman atheroma-associated cells

Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an imp ortant role in the pathogenesis of atherosclerosis. Moreover, atherosclerot ic lesions contain the Th1-type cytokine IFN-gamma, a potentiator of athero sclerosis. The present study demonstrates the differential expression of th e 3 IFN-gamma-inducible CXC chemokines - IFN-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell a chemoattrac tant (T-TAC) - by atheroma-associated cells, as well as the expression of t heir receptor, CXCR3, by all T lymphocytes within human atherosclerotic les ions in situ. Atheroma-associated endothelial cells (ECs), smooth muscle ce lls (SMCs), and macrophages (M phi) all expressed IP-10, whereas Mig and I- TAC were mainly expressed in ECs and M phi, as detected by double immunoflu orescence staining. ECs of microvessels within lesions also expressed abund ant I-TAC. In vitro experiments supported these results and showed that IL- 1 beta, TNF-alpha and CD40 ligand potentiated IP-10 expression from IFN-gam ma-stimulated ECs. In addition, nitric oxide (NO) treatment decreased IFN-g amma induction of IP-10. Our findings suggest that the differential express ion of IP-10, Mig, and I-TAG by atheroma-associated cells plays a role in t he recruitment and retention of activated T lymphocytes observed within vas cular wall lesions during atherogenesis.