title: Histamine H(1) receptor signaling regulates effector T cell responses and susceptibility to coxsackievirus B3-induced myocarditis.
abstract: Susceptibility to autoimmune myocarditis has been associated with histamine release by mast cells during the innate immune response to coxsackievirus B3 (CVB3) infection. To investigate the contribution of histamine H(1) receptor (H(1)R) signaling to CVB3-induced myocarditis, we assessed susceptibility to the disease in C57BL/6J (B6) H(1)R(-/-) mice. No difference was observed in mortality between CVB3-infected B6 and H(1)R(-/-) mice. However, analysis of their hearts revealed a significant increase in myocarditis in H(1)R(-/-) mice that is not attributed to increased virus replication. Enhanced myocarditis susceptibility correlated with a significant expansion in pathogenic Th1 and Vγ4(+) γδ T cells in the periphery of these animals. Furthermore, an increase in regulatory T cells was observed, yet these cells were incapable of controlling myocarditis in H(1)R(-/-) mice. These data establish a critical role for histamine and H(1)R signaling in regulating T cell responses and susceptibility to CVB3-induced myocarditis in B6 mice.
authors.affiliation: Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Laure K
authors.initials: LK
authors.lastname: Case
authors.forename: Mohamad
authors.initials: M
authors.lastname: Moussawi
authors.forename: Brian
authors.initials: B
authors.lastname: Roberts
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Noubade
authors.forename: Sally A
authors.initials: SA
authors.lastname: Huber
authors.forename: Cory
authors.initials: C
authors.lastname: Teuscher
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility; D029822:Enterovirus B, Human / Q000276:immunology*; D006632:Histamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
chemical_list: D011969:Receptors, Histamine H1; D006632:Histamine
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