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

Dimayuga, Paul C; Li, Hongyan; Chyu, Kuang-Yuh; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU ; Fishbein, Michael C; Shah, Prediman K and Cercek, Bojan (2005) In Arteriosclerosis, Thrombosis and Vascular Biology 25(Oct 13). p.2528-2534
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IFN-gamma, immune deficiency, mice, intimal thickening, Rag-1KO, lymphocytes
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
25
issue
Oct 13
pages
2528 - 2534
publisher
American Heart Association
external identifiers
  • wos:000233461500017
  • pmid:16224059
  • scopus:33644802641
ISSN
1524-4636
DOI
10.1161/01.ATV.0000190606.41121.00
language
English
LU publication?
yes
id
7d1dc936-c0f8-4bb0-be9d-3b85e8e852a5 (old id 144650)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16224059&dopt=Abstract
date added to LUP
2007-07-17 14:48:16
date last changed
2017-05-28 03:43:26
@article{7d1dc936-c0f8-4bb0-be9d-3b85e8e852a5,
  abstract     = {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 &lt; 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.},
  author       = {Dimayuga, Paul C and Li, Hongyan and Chyu, Kuang-Yuh and Nordin Fredrikson, Gunilla and Nilsson, Jan and Fishbein, Michael C and Shah, Prediman K and Cercek, Bojan},
  issn         = {1524-4636},
  keyword      = {IFN-gamma,immune deficiency,mice,intimal thickening,Rag-1KO,lymphocytes},
  language     = {eng},
  number       = {Oct 13},
  pages        = {2528--2534},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {T Cell Modulation of Intimal Thickening After Vascular Injury. The Bimodal Role of IFN-{gamma} in Immune Deficiency.},
  url          = {http://dx.doi.org/10.1161/01.ATV.0000190606.41121.00},
  volume       = {25},
  year         = {2005},
}