85
Views
11
CrossRef citations to date
0
Altmetric
Original

Effects of adenovirus-mediated gene transfer of ICOSIg and CTLA4Ig fusion protein on experimental autoimmune myocarditis

, , &
Pages 83-92 | Received 01 Sep 2005, Accepted 02 Dec 2005, Published online: 07 Jul 2009
 

Abstract

Objective: To explore the therapeutic alliance effects of adenovirus vector-mediated gene transfer of ICOSIg and CTLA4Ig fusion protein on experimental autoimmune myocarditis (EAM).

Methods: Expression vector pAdeno-CTLA4Ig and pAdeno-ICOSIg was constructed and transfected into HEK293 cells. Adenovirus expresses CTLA4Ig and ICOSIg was produced. Ad-CMV-GFP was used as controls. EAM was induced in Lewis rats by injection of procine cardiac myosin. All the immunized rats were divided into four groups. Group A (n = 15) received adenovirus containing CTLA4Ig and ICOSIg from day 14–28; group B (n = 15), group C (n = 15) and group D (n = 15) received adenovirus containing CTLA4Ig, ICOSIg and GFP, respectively. Group E (n = 10) was normal controls never received immunization. On day 28, all the rats were killed after echocardiography examination. Histopathological examination was used to observe inflammation in the myocardium. Western blot was used to detect CTLA4, ICOS, ICOSL and competitive RT-PCR for B7-1, B7-2 expression. T lymphocyte proliferation assay was performed and ELISPOT was used to detect the Th1 and Th2 production.

Results: Alliance application of CTLA4Ig and ICOSIg exerts therapeutic effects on EAM. After a treatment duration of 14 days, cardiac function and myocardial inflammation improved significantly compared to group D. Expression of CTLA-4, ICOS and ICOSL, B7-1 was statistically decreased in group A, B and C compared with group D. T-cell proliferation was inhibited by costimulatory blockade in a dose-dependent style. ICOSIg blockade significantly augments IL-4 and IL-10 production while diminished IFN-γ production.

Conclusions: Blockade of costimulatory pathway with alliance therapy of CTLA4Ig and ICOSIg alleviated autoimmune damage in EAM and improved cardiac function. The mechanisms may be downregulation of costimulatory molecules and anti-inflammation.

Acknowledgements

This study was supported by Harbin Medical University Postgraduate Creation Foundation (2005). We thank Prof. XIE Shu-sheng (Department of Immunology, Peking University) for kindly providing the plasmid containing human CTLA4Ig.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.