Abstract

Myocarditis frequently follows viral infections in both humans and experimental animals. However, growing evidence indicates cardiac injury results not from virus induced myolysis, but from T cell dependent immunopathogenic mechanisms. Male Balb/c mice infected with a myocarditic variant of coxsackievirus group B, type 3 (CVB3M) develop two distinct immune T cell populations involved in myocarditis. One recognizes antigens on uninfected myocytes (autoreactive cytolytic T lymphocyte, ACTL) and the other recognizes antigens on infected myocytes (virus specific cytolytic T lymphocyte, VSCTL). Evidence to date shows ACTL cause predominant myocardial injury in this mouse strain but ACTL sensitization in vivo depends upon a prior VSCTL response. VSCTL which belong to the 13T4+ (T helper) cell population, presumably produce lymphokines and induce either 1A expression on cardiocytes or infiltration of 1A+ inflammatory cells into the heart allowing myocyte antigen presentation to ACTL precursors. The goals of the present investigation are to characterize the antigens recognized by the two CTL populations and further elucidate the interactions of VSCTL and ACTL resulting in autoimmunity to heart antigens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028833-10
Application #
3340096
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1981-09-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405

  Publications

Hamrell, B B; Huber, S A; Leslie, K O (1995) Depressed unloaded sarcomere shortening velocity in acute murine coxsackievirus myocarditis: myocardial remodelling in the absence of necrosis or hypertrophy. Eur Heart J 16 Suppl O:31-5
Huber, S A; Moraska, A; Cunningham, M (1994) Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 mutants selected with monoclonal antibodies to group A streptococci. Proc Natl Acad Sci U S A 91:5543-7
Hamrell, B B; Huber, S A; Leslie, K O (1994) Reduced unloaded sarcomere shortening velocity and a shift to a slower myosin isoform in acute murine coxsackievirus myocarditis. Circ Res 75:462-72
Huber, S; Polgar, J; Moraska, A et al. (1993) T lymphocyte responses in CVB3-induced murine myocarditis. Scand J Infect Dis Suppl 88:67-78
Moraska, A; Huber, S A (1993) Synergism between adriamycin and coxsackie virus group B type 3 (CVB3) in induction of myocardial injury: potential role for gamma/delta TcR+ T lymphocytes in pathogenesis. Clin Immunol Immunopathol 68:124-8
Weller, A H; Hall, M; Huber, S A (1992) Polyclonal immunoglobulin therapy protects against cardiac damage in experimental coxsackievirus-induced myocarditis. Eur Heart J 13:115-9
Huber, S A (1992) Heat-shock protein induction in adriamycin and picornavirus-infected cardiocytes. Lab Invest 67:218-24
Frizelle, S; Schwarz, J; Huber, S A et al. (1992) Evaluation of the effects of low molecular weight heparin on inflammation and collagen deposition in chronic coxsackievirus B3-induced myocarditis in A/J mice. Am J Pathol 141:203-9
Huber, S A; Moraska, A; Choate, M (1992) T cells expressing the gamma delta T-cell receptor potentiate coxsackievirus B3-induced myocarditis. J Virol 66:6541-6
Weremeichik, H; Moraska, A; Herzum, M et al. (1991) Naturally occurring anti-idiotypic antibodies--mechanisms for autoimmunity and immunoregulation? Eur Heart J 12 Suppl D:154-7

Showing the most recent 10 out of 26 publications