Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12

Abstract Background : Human Herpes virus 6 (HHV-6) is a causative agent of exanthema subitum and replicates mainly in lymphocytes. The aim of present study was to investigate cytotoxicity against HHV-6-infected cells by cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC).

Methods : Human herpes virus 6-infected and -uninfected lymphocytes were used as target cells. Killing of target cells by CBMC and PBMC was investigated by the chromium release cytotoxicity assay.

Results : Freshly isolated CBMC and PBMC did not lyse HHV-6-infected and -uninfected cells. When CBMC and PBMC were cultured with interleukin (IL)-2, HHV-6-infected cells were significantly lysed compared with uninfected cells. Deletion of CD16⁺ cells by treatment of effector cells with anti- Leu-11b (CD16) antibody with complement reduced cytotoxicity against HHV-6-infected cells and T lymphocyte-rich cells did not lyse HHV-6-infected cells. Treatment of effector cells with anti-Fas ligand antibody and treatment of HHV-6-infected cells with anti-Fas antibody reduced cytotoxicity against HHV-6-infected cells. DNA fragmentation was detected in the supernatant from HHV-6-infected cells cultured with IL-2-activated lymphocytes. Culture of CBMC and PBMC with IL-12 also enhanced cytotoxicity against HHV-6-infected cells.

Conclusions : These data suggest that lymphocytes cultured with IL-2 or IL-12 mediate killing against HHV-6-infected cells and killing of HHV-6-infected cells was through apoptosis. Fas–Fas ligand interaction is one pathway by which HHV-6-infected cells are killed. Killing of HHV-6-infected cells by NK cells activated by cytokines may play a role in the recovery from HHV-6 infection in vitro.