Defective generation of killer cells against spontaneously Epstein-Barr virus (EBV)-transformed autologous B cells in a fatal EBV infection.

Killer cell activities were analysed in a 16-month-old boy with a sporadic form of fatal Epstein-Barr virus (EBV) infection, and compared with those in three patients with acute infectious mononucleosis (IM). We used spontaneously EBV-transformed autologous lymphoblastoid B cell lines (LCL) as target cells, because the results obtained with such targets can be expected to reflect most accurately the killer-versus-target reaction in vivo. The patient's fresh peripheral blood mononuclear cells (PBMC) had relatively high natural killer (NK) cell activity against K562 cells (128% of the control value), but they did not kill his autologous LCL. The patient's PBMC, unlike PBMC of acute IM, showed no cytotoxicity against Raji cells and autologous LCL after 5 days' culture in the presence of recombinant interleukin 2 (rIL-2), indicating defective generation of lymphokine-activated killer (LAK) cells. The patient's PBMC, unlike PBMC of acute IM, also could not induce cytotoxicity against autologous LCL when cocultured with mitomycin C-treated respective autologous LCL for 7 days. The addition of rIL-2 to the culture significantly restored their ability to generate cytotoxic T lymphocytes (CTL) against his LCL: the percent cytotoxicity value rose from 3.0% to 37.7%. With respect to this, the endogenous IL-2 production by the patient's PBMC was deficient. These results suggest that the defective EBV-selective CTL generation was due to deficient IL-2 production. The failure of the killer cells to eliminate EBV-infected cells seems to have been responsible for the patient's unusual course after primary EBV infection.