Amelioration of myocarditis by HVEM-overexpressing dendritic cells through induction of IL-10-producing cells.

Abstract:

AIMS:Herpes virus entry mediator (HVEM) is considered to be a molecular 'switch' for immune responses, and a role in immune modification has been reported. The aim of this study was to assess whether HVEM-mediated immune suppression could protect against experimental autoimmune myocarditis (EAM) induced by myosin. METHODS AND RESULTS:We constructed HVEM-expressing adenovirus (AdHVEM) and fusion protein HVEM-Ig and evaluated their roles in immunoregulation in vitro and in vivo. Immunoregulation of dendritic cells (DCs) infected with recombinant virus or treated with HVEM-Ig was then studied. DCs transfected with AdHVEM (DC-AdHVEM) were protected against EAM, whereas HVEM-Ig had no protective effect. Further study showed that DC-AdHVEMs produced a regulatory cytokine, IL-10, which had further effects on induction of IL-10 producing CD4(+) T cells. This subset of T cells was then responsible for the protection against EAM. CONCLUSION:Myosin-DC-AdHVEM cell gene therapy appears to be a safe and effective way of inhibiting the development of EAM. The signal induced by HVEM seems to play different roles in different cells.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Cai G,Wang H,Qin Q,Zhang J,Zhu Z,Liu M,Shen Q

doi

10.1093/cvr/cvp219

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

425-33

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvp219

journal_volume

84

pub_type

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