Lymphokine activated killer cells in murine coxsackievirus B3 myocarditis

The purpose of the present study was to determine whether lymphokine activated killer (LAK) cells were involved in the development of coxsackievirus B3 (CB3) myocarditis in both the acute viremic (Experiment I) and the subacute aviremic (Experiment II) stages. To induce LAK cells, recombinant human interleukin-2 (IL-2) was administered to CB3-infected mice subcutaneously daily, starting on day 0 in Experiment I and on day 7 in Experiment II for 7 days, respectively. The treated groups were compared to infected controls. Splenic lymphocytes of IL-2 treated mice were further cultured in vitro in IL-2 containing medium for 7 days, and LAK cell activity, i.e., cytotoxic activity of the lymphocytes against EL-4 tumor cells and against cultured fetal myocytes, was assayed by⁵¹Cr-release method. In Experiment I, histologic scores, myocardial virus titers, and LAK cell activity did not differ significantly between IL-2 treated and untreated groups. In contrast, in Experiment II, there were more cellular infiltration associated with severe necrosis and higher LAK cell activity against EL-4 cells and cultured myocytes in IL-2 treated than in untreated groups. The presence of LAK cells was demonstrated in the subacute stage of murine CB3 myocarditis. Thus, the behavior of LAK cell activity may vary with the course of myocarditis, and enhanced LAK cell activity may be involved in the development of the disease.This work was supported by research grants from the Conference on Coronary Artery Disease, Japanese Education of Science and Walfare (Nos. 08877110 and 09470164), Kanae Shinyaku Foundation, and Japan Cardiovascular Research Foundation.