T-cell receptor Vβ8. 1 peptide reduces coxsackievirus-induced cardiopathology in aged mice
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Viral myocarditis is an important cause of heart failure and cardiomyopathy. Immunosenescence, characterized by a dramatic reduction in immune responsiveness, can increase susceptibility to cardiopathology from viral infections. The T-cell receptor (TCR) Vβ 8.1 peptide, a 16-merpeptide, has shown immuno-regulating and immunostimulating effects in viral-induced immunodeficiency. In our study, 18-mo-old C57BI/6 female mice were treated twice with TCR Vβ8.1 peptide and 10 d before sacrifice were injected ip with coxsackievirus B3. Cardiac histopathology was assessed for lesion severity. Splenocyte cytokine production (interleukin-2,-4,-6, interferon-γ) and heart viral titers were determined. Our data suggest that immunosenescence suppressed both T helper (Th1) and Th2 cytokine production and that treatment with TCR Vβ8.1 peptide induced cytokine stimulation close to levels seen in young mice. Nontreated aged mice developed some degree of myocarditis (75% mild and 25% severe), whereas only 35% of the peptide-treated aged group developed cardiopathology, with 25% being mild and 10% severe. Heart tissue from nontreated aged mice infected with coxsackievirus had a higher viral titer than hearts of aged mice equally infected but treated with the peptide. In conclusion, TCR Vβ8.1 peptide induced immunoregulation, and inhibited or reduced coxsackievirus B3-induced, cardiopathology in aged mice.
Key WordsImmunosenescence age peptide therapy TCR coxsackievirus cardiopathology myocarditis Th1 Th2 cytokines
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