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.


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.


CONCLUSIONS
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.
Dimayuga
Paul C
PC
Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA. DimayugaP@cshs.org
Li
Hongyan
H
Chyu
Kuang-Yuh
KY
Fredrikson
Gunilla Nordin
GN
Nilsson
Jan
J
Fishbein
Michael C
MC
Shah
Prediman K
PK
Cercek
Bojan
B
D019264:Adoptive Transfer; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D020212:Carotid Artery Injuries / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D015870:Gene Expression / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000502:physiology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D050856:Interferon Regulatory Factor-1; D011994:Recombinant Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C064658:RAG-1 protein; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse