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

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... was reduced by T cell transfer (PϽ0.01). 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. (Arterioscler Thromb Vasc Biol. 2005;25:2528-2534.) Key Words: IFN-␥ Ⅲ immune deficiency Ⅲ intimal thickening Ⅲ lymphocytes Ⅲ Rag-1KO mice T Cell Reconstitution Splenocytes from age-matched wild-type (WT) mice were isolated as previously described. 2 Aliquots of the cells were cultured in RPMI/