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.

T-cell receptor V beta 8.1 peptide reduces coxsackievirus-induced cardiopathology during murine acquired immunodeficiency syndrome.

Infection of people with human immunodeficiency virus (HIV) as well as LP-BM5 infection in mice results in progressive deterioration of the immune system in the majority of untreated hosts. Peptide immunotherapy has been shown to be effective in the stimulation or immunoregulation of T-helper 1 (T(H)1) and T-helper 2 (T(H) 2) response subsets. In murine acquired immunodeficiency syndrome (AIDS), T(H)1 deficiency enables the host to be susceptible to coxsackievirus infection, inducing cardiopathology in a short period. T-cell receptor (TCR) Vbeta8.1 peptide, a 16-mer peptide containing the entire CDR1 segment and part of the FR2 region of human Vbeta8, showed both an immunoregulating and immunostimulating effect in murine AIDS. TCR Vbeta8.1 peptide acts on T cells promoting interleukin-2 production and therefore enhancing a cell-mediated immune response. It retarded development of cardiopathology due to coxsackievirus infection. Retrovirus-infected mice treated with the peptide showed a longer life span than the nontreated, retrovirus-infected animals.