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The role of T helper 1 and T helper ...

Afanasyeva, Marina G.

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The role of T helper 1 and T helper 2 cytokines in murine experimental autoimmune myocarditis.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The role of T helper 1 and T helper 2 cytokines in murine experimental autoimmune myocarditis./
作者:	Afanasyeva, Marina G.
面頁冊數:	243 p.
附註:	Adviser: Noel R. Rose.
Contained By:	Dissertation Abstracts International63-03B.
標題:	Biology, Animal Physiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046410
ISBN:	0493605479

The role of T helper 1 and T helper 2 cytokines in murine experimental autoimmune myocarditis.
Afanasyeva, Marina G.

The role of T helper 1 and T helper 2 cytokines in murine experimental autoimmune myocarditis. - 243 p.

Adviser: Noel R. Rose.

Thesis (Ph.D.)--The Johns Hopkins University, 2002.

Autoimmunity is believed to play an important role in many cases of human myocarditis. However, the exact mechanisms of immune-mediated damage to the heart in this disease are not fully elucidated. The role of cytokines, particularly those involved in T helper (Th) 1 and Th2 immune responses, remains unknown. The goal of this work was to explore the role of Th1 and Th2 cytokines in a murine model of cardiac myosin-induced experimental autoimmune myocarditis (EAM). Analysis of the histologic and antibody profiles in EAM revealed a Th2 phenotype and suggested that interleukin-4 (IL-4), the key Th2 cytokine, plays a pathogenic role in this disease. In support of the disease-promoting role of IL-4, anti-IL-4 monoclonal antibody (mAb) treatment reduced the severity of EAM and induced a shift from a Th2 to a Th1 phenotype. To investigate the role of IL-12, the key Th1-promoting cytokine, studies were undertaken using mice deficient in IL-12 receptor (IL-12R) signaling, IL-12R1 knockout (KO) and STAT4 KO mice. Both types of KO mice were resistant to the induction of myocarditis, while treatment with exogenous IL-12 exacerbated disease. Since IFN-γ is believed to be responsible for many actions of IL-12, its role was investigated using three approaches: depleting IFN-γ with a mAb, using IFN-γ KO mice, or treating mice with exogenous IFN-γ. These experiments demonstrated that IFN-γ has a disease-limiting role in EAM and therefore does not mediate the disease-promoting effects of IL-12. Studies of T cell responses in EAM showed that the absence of IFN-γ leads to the expansion of activated/memory T cells and to the reduction in the number of T cells undergoing apoptosis, suggesting a potential disease-suppressive mechanism of IFN-γ. Assessment of the left ventricular function using pressure-volume analysis revealed that IFN-γ KO mice have a higher frequency of progression to dilated cardiomyopathy and congestive heart failure compared to WT mice. Furthermore, IFN-γ KO, but not WT, mice developed a restrictive/constrictive hemodynamic profile that was associated with the presence of grossly detectable adhesive fibrous pericarditis. Thus, these results demonstrate that IFN-γ plays a critical role in limiting the severity of myocarditis thereby preventing complications such as cardiomyopathy, heart failure, and pericarditis. EAM in IFN-γ KO mice represents a novel and unique animal model of constrictive pericarditis.

ISBN: 0493605479Subjects--Topical Terms:

1017835
Biology, Animal Physiology.

The role of T helper 1 and T helper 2 cytokines in murine experimental autoimmune myocarditis.
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