γδ+ T cells regulate major histocompatibility complex class II (IA and IE)-dependent susceptibility to coxsackievirus B3-induced autoimmune myocarditis

S. A. Huber, J. E. Stone, D. H. Wagner, J. Kupperman, L. Pfeiffer, C. David, R. L. O'Brien, G. S. Davis, M. K. Newell

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Coxsackievirus B3 (CVB3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. C57BL/6 mice, which inherently lack major histocompatibility complex (MHC) class II IE antigen, develop minimal cardiac lesions despite high levels of virus in the heart. The present experiments evaluate the relative roles of class II IA and IE expression on myocarditis susceptibility in four transgenic C57BL/6 mouse strains differing in MHC class II antigen expression. Animals lacking MHC class II IE antigen (C57BL/6 [IA+ IE-] and AB(intersection set) [IA- IE- ]) developed minimal cardiac lesions subsequent to infection despite high concentrations of virus in the heart. In contrast, strains expressing IE (AB(o) Eα [IA- IE+] and Bl.Tg.Eα [IA+ IE+]) had substantial cardiac injury. Myocarditis susceptibility correlated to a Th1 (gamma interferon- positive) cells response in the spleen, while disease resistance correlated to a preferential Th2 (interleukin-4-positive) phenotype. Vγ/Vδ analysis indicates that distinct subpopulations of γδ+ T cells are activated after CVB3 infection of C57BL/6 and Bl.Tg.Eα mice. Depletion of γδ+ T cells abrogated myocarditis susceptibility in IE+ animals and resulted in a Th1→Th2 phenotype shift. These studies indicate that the MHC class II antigen haplotype controls myocarditis susceptibility, that this control is most likely mediated through the type of γδ T cells activated during CVB3 infection, and finally that different subpopulations of γδ+ T cells may either promote or inhibit Th1 cell responses.

Original languageEnglish (US)
Pages (from-to)5630-5636
Number of pages7
JournalJournal of virology
Volume73
Issue number7
StatePublished - Jun 23 1999

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Huber, S. A., Stone, J. E., Wagner, D. H., Kupperman, J., Pfeiffer, L., David, C., O'Brien, R. L., Davis, G. S., & Newell, M. K. (1999). γδ+ T cells regulate major histocompatibility complex class II (IA and IE)-dependent susceptibility to coxsackievirus B3-induced autoimmune myocarditis. Journal of virology, 73(7), 5630-5636.