1998 Volume 12 Issue 6 Pages 406-416
Serological observations of patients with IgG2 deficiency have shown frequent occurrence of abnormal patterns of antibodies to Epstein-Barr virus (EBV). To elucidate this mechanism, we studied the immunological functions of seven patients. Four had unusual EBV serological profiles ; three of the seven were two half-brothers and their mother. The lymphocyte subsets, nonspecific killer activity, and lymphocyte proliferative responses were determined by flow cytometry, 51Cr-release assay, and [3H] thymidine incorporation assay, respectively. The cytotoxic T-cell responses to autologous EBV-infected cells were further analyzed in a 51Cr-release assay, in combination with cell depletion and cold-target inhibition assays. Although four of the patients with abnormal serological profiles for EBV had low CD4/CD8 ratios (<1.0), their nonspecific killer activity and lymphocyte proliferative responses were normal. The lymphocytes stimulated with autologous EBV-infected cells had a defect in their ability to kill the autologous cells : The percent lysis values (mean±SD) were decreased (5.8%±1.5%) in the four patients, compared with the control values of 20.8%±4.5%. There was no such defect of EBV-specific cytotoxic T cells in the other three patients. Phenotypic and functional analyses of the cytotoxic T cells demonstrated that the decrease in killing ability was, at least in part, caused by a defective generation of the EBV-specific cytotoxic CD8+ T cells. The present study indicates that a portion of IgG2 deficiency patients develop atypical EBV infection because of the defective cytotoxic T-cell response to EBV. It would appear that this disorder is, in part, a combined immunodeficiency characterized by IgG2 deficiency and defective cellular immunity against EBV.
