Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice

Abstract

The efficacy of monoclonal antibodies against T cell subsets in the therapy of experimental myocarditis caused by coxsackievirus B3 (CB3) was investigated. Two-week-old male C3H/He mice were inoculated with CB3 virus. Treatment was begun in the viremic stage (starting on the day of inoculation) in experiment 1 and in the later aviremic stage (starting on day 10) in experiment 2. Rat anti-mouse monoclonal antibodies, Lyt 1 (helper/inducer T) at 1 μg/mouse (group 2 in experiment 1; group 6 in experiment 2), Lyt 2 (suppressor/cytotoxic T) at 1 μg/mouse (group 3 in experiment 1; group 7 in experiment 2), and Lyt 1 at 1 μg plus Lyt 2 at 1 μg/mouse (group 4 in experiment 1; group 8 in experiment 2), were administered subcutaneously daily for 2 weeks. The treatment groups were compared with infected controls (group 1 in experiment 1; group 5 in experiment 2). In experiment 1, the survival rate in group 4 was higher (p < 0.01) than in group 1. In experiment 2, mice treated with Lyt 1 plus Lyt 2 (group 8) survived significantly longer (p < 0.05) than did controls (group 5). In experiment 1, myocardial virus titers on days 5 and 6 did not show any significant differences among the four groups. Serum-neutralizing antibody titers between group 1 and group 4 in experiment 1 or between group 5 and group 8 in experiment 2 did not differ significantly. Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups: there was less infiltration in group 4 and in group 8 and less severe necrosis in group 8. The in vivo efficacy of the administered monoclonal antibodies was shown by immunostaining methods in uninfected mice receiving the same treatment as in experiment 1. Thus, monoclonal antibody therapy for total T cells, but not for each T cell subset, partially suppressed acute myocarditis in mice, independent of mycoardial CB3 virus replication.