on October 13, 2005
Published online before print October 13, 2005, doi: 10.1161/01.ATV.0000190606.41121.00
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Submitted on February 3, 2005
Accepted on September 28, 2005
T Cell Modulation of Intimal Thickening After Vascular Injury. The Bimodal Role of IFN-
in Immune Deficiency
Paul C. Dimayuga *;
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.
* To whom correspondence should be addressed. 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.
Key words: IFN-
•
immune deficiency •
intimal thickening •
lymphocytes •
Rag-1KO mice
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