Apoptosis of CD4+ T lymphocytes in human herpesvirus-6 infection

The present authors have recently reported that inoculation with human herpesvirus-6 (HHV-6) renders CD4+ T lymphocytes susceptible to apoptosis in vitro. In order to confirm that apoptosis of CD4+ T lymphocytes also occurs in HHV-6 infection in vivo, apoptosis of lymphocytes isolated from nine patients with exanthem subitum and from an adult patient with severe HHV-6 infection was examined. Peripheral blood mononuclear cells were cultured for 3 days and apoptosis of lymphocytes was then examined by flow cytometry of propidium iodide-stained DNA. The percentages of hypodiploid DNA, indicating apoptosis, in lymphocytes from 10 patients with HHV-6 infection were significantly higher than those from five infant patients with noninfectious diseases and five healthy adults (P < 0-0002). DNA fragmentation was also detected by agarose gel electrophoresis in lymphocytes from patients with HHV-6 infection. Apoptosis appeared to occur predominantly in CD4+ T lymphocytes and HHV-6 was isolated from the CD4+ T lymphocyte fraction. These data demonstrate that HHV-6 renders CD4+ T lymphocytes susceptible to apoptosis in vivo.