T cells expressing the gamma delta T-cell receptor potentiate coxsackievirus B3-induced myocarditis.
Initial studies determined whether intraperitoneal (i.p.) injection of BALB/c mice with 0.1, 1.0, and 10 mg of adriamycin (a cardiotoxic anthracycline antibiotic) for times ranging between 1 and 9 weeks prior to i.p. injection of 10(5) PFU of coxsackievirus B3 (CVB3) would alter the severity of virus-induced myocarditis. Prior adriamycin exposure enhanced pathogenicity of a poorly pathogenic CVB3 variant (H310A1) but had no effect on myocarditis produced by the pathogenic variant (H3). Cardiac virus concentrations were equivalent in H3- and H310A1-infected mice irrespective of adriamycin treatment. BALB/c mice treated with either 0.1 ml of complete Freund's adjuvant (CFA), 10 mg of adriamycin, or 10(5) PFU of H3 and H310A1 i.p. developed cytolytic Thy 1.2+ lymphocytes (CTL) to H3-infected myocytes 7 days later. CFA-, adriamycin-, and H3-treated mice developed CTL expressing the gamma delta+ T-cell receptors, while H310A1-infected animals did not. Only H3- and H310A1-infected mice developed alpha beta+ CTL. Treatment of BALB/c mice with 0.1 ml of CFA 5 days prior to H310A1 infection dramatically increased myocarditis. Selective depletion of gamma delta+ T cells abrogated this effect. The ability of gamma delta+ T cells to augment the pathogenicity of H310A1 infection was confirmed by adoptive transfer of CFA-stimulated T cells depleted of either gamma delta- or gamma delta+ cells into H310A1-infected recipients.
Huber
S A
SA
Department of Pathology, University of Vermont, Burlington 05405-0068.
Moraska
A
A
Choate
M
M
D000818:Animals; D000831:Animals, Newborn; D002469:Cell Separation; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity*; D005620:Freund's Adjuvant / Q000276:immunology; D006321:Heart / Q000187:drug effects / Q000382:microbiology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000378:metabolism / Q000382:microbiology*; D009206:Myocardium / Q000166:cytology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014774:Virulence
D016692:Receptors, Antigen, T-Cell, gamma-delta; D004317:Doxorubicin; D005620:Freund's Adjuvant