1. Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, and the Departments of
2. Surgery,
3. Dermatology,
4. Pathology and
5. Immunobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA

Correspondence to: George Tellides^1,2 Correspondence and requests for materials should be addressed to G.T. (e-mail: Email: george.tellides@yale.edu).

Abstract

Atherosclerosis and post-transplant graft arteriosclerosis are both characterized by expansion of the arterial intima as a result of the infiltration of mononuclear leukocytes, the proliferation of vascular smooth muscle cells (VSMCs) and the accumulation of extracellular matrix^{1, 2, 3}. They are also associated with the presence of the immunomodulatory cytokine interferon- (IFN-)^{2, 3}. Moreover, in mouse models of atheroma formation or allogeneic transplantation, the serological neutralization⁴ or genetic absence^{5, 6, 7, 8} of IFN- markedly reduces the extent of intimal expansion. However, other studies have found that exogenous IFN- inhibits cultured VSMC proliferation^{9, 10, 11, 12, 13, 14} and matrix synthesis¹⁵, and reduces intimal expansion in response to mechanical injury^{16, 17, 18}. This discrepancy is generally explained by the idea that IFN- either directly activates macrophages, or, by increasing antigen presentation, indirectly activates T cells within the lesions of atherosclerosis and graft arteriosclerosis. These activated leukocytes are thought to express the VSMC-activating cytokines^{1, 2, 3} and cell-surface molecules¹⁹ that cause the observed arteriosclerotic responses. Here we have inserted pig and human arteries into the aorta of immunodeficient mice, and we show that IFN- can induce arteriosclerotic changes in the absence of detectable immunocytes by acting on VSMCs to potentiate growth-factor-induced mitogenesis.