Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice
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Abstract:
DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect.
Insights
Coxsackievirus B-3 infection in mice causes myocarditis and pancreatitis, primarily mediated by CD4+ T cells. These T cells target heart cells, leading to organ damage, while liver infection shows no injury.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Coxsackievirus B-3 (CVB3) infection can lead to significant organ damage.
- The specific immune mechanisms driving CVB3-induced myocarditis and pancreatitis are not fully understood.
- T lymphocyte subpopulations play a critical role in viral pathogenesis and organ-specific injury.
Purpose of the Study:
- To elucidate the role of T lymphocyte subpopulations in CVB3-induced myocarditis and pancreatitis.
- To identify the specific cellular targets and immune mechanisms responsible for CVB3-mediated organ damage.
- To investigate the involvement of major histocompatibility complex (MHC) antigens in T cell-mediated viral injury.
Main Methods:
- DBA/2 male mice were inoculated with CVB3, and T lymphocyte subpopulations were selectively depleted.
- Immune lymphocytes from CVB3-infected mice were adoptively transferred into T cell-deficient recipients.
- Cell adhesion assays using myocyte, fibroblast, and liver vascular endothelial cell (VEC) monolayers were performed, with or without MHC blocking antibodies.
Main Results:
- CVB3 inoculation led to myocarditis and pancreatitis, with CD4+ T cells identified as key mediators of tissue damage.
- Adoptive transfer of unfractionated immune lymphocytes or cells eluted from heart monolayers induced myocarditis and pancreatitis.
- Pathogenicity was associated with T cell adherence to myocytes, mediated by class II MHC antigens, but not fibroblasts or liver VECs.
Conclusions:
- CD4+ T cells are critical effectors of CVB3-induced myocarditis and pancreatitis in DBA/2 mice.
- The interaction between pathogenic T cells and cardiac myocytes, involving class II MHC, is crucial for viral myocarditis development.
- CVB3 infection can lead to viral replication in multiple organs without causing apparent tissue injury, highlighting organ-specific immune responses.