T-cell receptor vbeta8.1 peptide reduces coxsackievirus-induced cardiopathology in aged mice.
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) Vbeta 8.1 peptide, a 16-mer peptide, has shown immuno-regulating and immunostimulating effects in viral-induced immunodeficiency. In our study, 18-mo-old C57Bl/6 female mice were treated twice with TCR Vbeta8.1 peptide and 10 d before sacrifice were injected ip with coxsackievirus B3. Cardiac histopathology was assessed for lesion severity. Splenocyte cyto-kine production (interleukin-2, -4, -6, interferon-gamma) 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 Vbeta8.1 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 Vbeta8.1 peptide induced immunoregulation, and inhibited or reduced coxsackievirus B3-induced cardiopathology in aged mice.
Sepúlveda
Ramón Tomás
RT
Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Marchalonis
John Jacob
JJ
Watson
Ronald Ross
RR
D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000473:pathology; D004770:Enterovirus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D010446:Peptide Fragments / Q000627:therapeutic use*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000627:therapeutic use*
D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C075784:T cell receptor Vbeta8