EPSTEIN-BARR-VIRUS-INFECTED B-CELLS OF MALES WITH THE X-LINKED LYMPHOPROLIFERATIVE SYNDROME STIMULATE AND ARE SUSCEPTIBLE TO T-CELL-MEDIATED LYSIS

Primary infection with the Epstein-Barr virus (EBV) results in fatal i nfectious mononucleosis in up to 70% of males affected by the X-linked lymphoproliferative syndrome (XLP), This rare disease is often associ ated with diverse natural killer (NK)-, B- and T-cell deficiencies. We describe experiments testing whether the B lymphocytes of affected ma les play a role in the pathogenesis of XLP due to a low susceptibility to T-cell-mediated immunity. Using reverse transcription-polymerase c hain reaction (RT-PCR) and immunohistochemistry we detected in these B cells the expression of viral proteins EBNA-1, EBNA-2, EBNA-3A, EBNA- 3C, LMP-1 and LMP-ZA, which provide targets for cytotoxic T cells. Maj or histocompatibility complex (MHC) class I, MHC class II and the B7 c ostimulatory molecule were present on the cell surface. Accordingly, t he EBV-infected B cells were lysed in Cr-51-release assays by T lympho cytes sharing MHC determinants with the targets. This MHC-restricted a nd specific lysis was confirmed in competition experiments using MHC-s pecific monoclonal antibodies (MAbs) and synthetic peptides. XLP-deriv ed LCLs could also induce MHC class I-restricted memory and cytotoxic T lymphocytes. Thus, these XLP-derived B cells resembled normal LCls i n vitro with respect to induction of EBV-specific cytotoxic T cells (C TL), the ability to present EB viral antigens and the susceptibility t o EBV-specific and MHC-restricted CTL-mediated killing. The failure of the immune system to eliminate these virus-infected B cells in XLP is clearly not caused by a B-cell-specific defect. (C) 1998 Wiley-Liss, Inc.