T Cell Modulation of Intimal Thickening After Vascular Injury. The Bimodal Role of IFN-{gamma} in Immune Deficiency.

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-gamma 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-gamma starting on the day of injury inhibited intimal thickening in Rag-1KO mice. However, antibody neutralization of endogenous IFN-gamma in Rag-1KO mice starting 7 days after injury decreased intimal thickening, indicating that late presence of IFN-gamma promoted intimal thickening in Rag-1KO mice. Results further suggest that the effect of late IFN-gamma 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-gamma secretion. In the Rag-1KO mice, late IFN-gamma expression promotes intimal thickening. These findings add novel insight to conditions of immune deficiency that affect intimal thickening.