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003 OCoLC;

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035 a| (Sirsi) o973414695;

035 a| (OCoLC)973414695;

049 a| EREE;

100 1 a| Reece, Shaun Patrick,e| author.?| UNAUTHORIZED;

245 10 a| Modulation of experimental autoimmune myocarditis with cytokine-myosin fusion proteins and novel cardiac peptides /c| by Shaun Patrick Reece.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2016.;

300 a| 143 pages :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 3.58 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph. D.c| East Carolina Universityd| 2016;

500 a| Presented to the faculty of the Department of Physiology.;

500 a| Advisor: Robert Lust.;

500 a| Title from PDF t.p. (viewed March 29, 2017).;

520 3 a| Infectious agents that induce cross-reactive myocarditic T cell responses may cause autoimmune inflammation of the heart, dilated cardiomyopathy (DCM), and heart failure. The purpose of this study was to evaluate the efficacy of GMCSF-Myosin fusion proteins as tolerogenic vaccines capable of inhibiting experimental autoimmune myocarditis (EAM). The fusion proteins were comprised of an N-terminal granulocyte macrophage-colony stimulating factor (GM-CSF) domain and a C-terminal cardiac myosin antigen domain. The antigenic domains Myosin 1052-1076 and Myosin 614-643 were chosen based on epitopes known to cause EAM in Lewis rats and BALB/c mice, respectively. Bioactivity of the cytokine domains for GMCSF-Myo1052 and GMCSF-Myo614 were confirmed with bone marrow proliferation assays. Enhanced antigen presentation was confirmed for GMCSF-Myo1052. Both fusion proteins were found to inhibit disease progression when given as a pretreatment before EAM induction. When administered after disease induction, GMCSF-Myo614 reduced the incidence of EAM. To investigate the mechanisms of these tolerogenic vaccines, a model of EAM was developed in C57BL/6 mice by evaluating a peptide (myosin 718-736) derived from the murine cardiac alpha myosin heavy chain and theorized to bind to H2-I-Ab. EAM was successfully induced in Interferon gamma receptor knockout (Ifgr1-/- ) mice on the C57BL/6 background. Defining the mechanisms by which Interferon-gamma (IFN-[gamma]) inhibits EAM on the C57BL/6 background is beyond the scope of this project, but it is hypothesized that T cell apoptosis or induction of T regulatory cells is involved. In conclusion, this study demonstrated the feasibility of using GMCSF-Myosin fusion proteins to inhibit EAM, and provides a new model of EAM on C57BL/6 background to explore the mechanisms by which GMCSF-Myosin fusion proteins mediate tolerance.;

504 a| Includes bibliographical references.;

650 2 a| Myocarditis.=| ^A938005;

650 2 a| Cytokines.=| ^A926007;

650 2 a| Heart.=| ^A917646;

650 2 a| Peptides.=| ^A918705;

650 2 a| Myosins.=| ^A939365;

653 a| Experimental autoimmune myocarditis;

653 a| Fusion proteins;

653 a| Cardiac peptides;

700 1 a| Lust, Robert M.,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Physiology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6077;

949 o| wjh;

994 a| C0b| ERE;

096 a| WG 280;

596 a| 1 4;

998 a| 4627389;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4627389-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 2/22/2017x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4627389-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 2/22/2017x| ETDz| HERESOURCE;

Modulation of experimental autoimmune myocarditis with cytokine-myosin fusion proteins and novel cardiac peptides / by Shaun Patrick Reece.

Author/creator	Reece, Shaun Patrick author.
Other author	Lust, Robert M., degree supervisor.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2016.
Description	143 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Myocarditis. Cytokines. Heart. Peptides. Myosins.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Infectious agents that induce cross-reactive myocarditic T cell responses may cause autoimmune inflammation of the heart, dilated cardiomyopathy (DCM), and heart failure. The purpose of this study was to evaluate the efficacy of GMCSF-Myosin fusion proteins as tolerogenic vaccines capable of inhibiting experimental autoimmune myocarditis (EAM). The fusion proteins were comprised of an N-terminal granulocyte macrophage-colony stimulating factor (GM-CSF) domain and a C-terminal cardiac myosin antigen domain. The antigenic domains Myosin 1052-1076 and Myosin 614-643 were chosen based on epitopes known to cause EAM in Lewis rats and BALB/c mice, respectively. Bioactivity of the cytokine domains for GMCSF-Myo1052 and GMCSF-Myo614 were confirmed with bone marrow proliferation assays. Enhanced antigen presentation was confirmed for GMCSF-Myo1052. Both fusion proteins were found to inhibit disease progression when given as a pretreatment before EAM induction. When administered after disease induction, GMCSF-Myo614 reduced the incidence of EAM. To investigate the mechanisms of these tolerogenic vaccines, a model of EAM was developed in C57BL/6 mice by evaluating a peptide (myosin 718-736) derived from the murine cardiac alpha myosin heavy chain and theorized to bind to H2-I-Ab. EAM was successfully induced in Interferon gamma receptor knockout (Ifgr1-/- ) mice on the C57BL/6 background. Defining the mechanisms by which Interferon-gamma (IFN-[gamma]) inhibits EAM on the C57BL/6 background is beyond the scope of this project, but it is hypothesized that T cell apoptosis or induction of T regulatory cells is involved. In conclusion, this study demonstrated the feasibility of using GMCSF-Myosin fusion proteins to inhibit EAM, and provides a new model of EAM on C57BL/6 background to explore the mechanisms by which GMCSF-Myosin fusion proteins mediate tolerance.
General note	Presented to the faculty of the Department of Physiology.
General note	Advisor: Robert Lust.
General note	Title from PDF t.p. (viewed March 29, 2017).
Dissertation note	Ph. D. East Carolina University 2016
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Modulation of experimental autoimmune myocarditis with cytokine-myosin fusion proteins and novel cardiac peptides / by Shaun Patrick Reece.

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