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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2528.)
© 2005 American Heart Association, Inc.

Vascular Biology

T Cell Modulation of Intimal Thickening After Vascular Injury

The Bimodal Role of IFN- in Immune Deficiency

Paul C. Dimayuga; Hongyan Li; Kuang-Yuh Chyu; Gunilla Nordin Fredrikson; Jan Nilsson; Michael C. Fishbein; Prediman K. Shah; Bojan Cercek

From Atherosclerosis Research Center (P.C.D., H.L., K.-Y.C., P.K.S., B.C.), Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA and the Department of Pathology (M.C.F.), David Geffen School of Medicine at UCLA, Los Angeles, Calif; and Experimental Cardiovascular Research (G.N.F., JN.), Department of Medicine, Lund University, University Hospital MAS, Malmö, Sweden.

Correspondence to Paul C. Dimayuga, PhD, Cedars-Sinai Medical Center, Davis 1064, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail DimayugaP{at}cshs.org

Background— Immune deficiency results in exuberant intimal thickening after arterial injury. The mechanisms involved are not well defined. We investigated the role of T cells and IFN- in the response to injury in normal and immune-deficient Rag-1KO mice.

Methods and Results— Carotid arterial injury was induced in wild-type (WT), Rag-1KO mice, and Rag-1KO mice reconstituted with T cell-enriched splenocytes. The exuberant intimal thickening in Rag-1KO mice compared with WT mice 21 days after injury was reduced by T cell transfer (P<0.01). Exogenous IFN- starting on the day of injury inhibited intimal thickening in Rag-1KO mice. However, antibody neutralization of endogenous IFN- in Rag-1KO mice starting 7 days after injury decreased intimal thickening, indicating that late presence of IFN- promoted intimal thickening in Rag-1KO mice. Results further suggest that the effect of late IFN- in Rag-1KO mice is mediated in part by increased IRF-1 and iNOS expression, coupled with low SOCS1 expression.

Conclusion— T cells inhibit intimal thickening in the early stages of the response to injury through basal IFN- secretion. In the Rag-1KO mice, late IFN- expression promotes intimal thickening. These findings add novel insight to conditions of immune deficiency that affect intimal thickening.

Immune deficiency results in exuberant intimal thickening after arterial injury. We investigated the modulatory role of T cells and IFN- in the response to injury in normal and immune-deficient Rag-1KO mice. The study adds novel insight in defining factors that contribute to vascular disease in conditions of immune deficiency.

Key Words: IFN- • immune deficiency • intimal thickening • lymphocytes • Rag-1KO mice

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