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Epstein‐Barr virus‐infected B cells of males with the X‐linked lymphoproliferative syndrome stimulate and are susceptible to T‐cell‐mediated lysis
Author(s) -
Jäger Michael,
BenningerDöring Gerlinde,
Prang Nadja,
Sylla Bakary S.,
Laumbacher Barbara,
Wank Rudolf,
Wolf Hans,
Schwarzmann Fritz
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980529)76:5<694::aid-ijc14>3.0.co;2-4
Subject(s) - lysis , virus , epstein–barr virus , virology , biology , immunology , lymphoproliferative disorders , cell , herpesviridae , b cell , medicine , lymphoma , viral disease , antibody , genetics
Primary infection with the Epstein‐Barr virus (EBV) results in fatal infectious mononucleosis in up to 70% of males affected by the X‐linked lymphoproliferative syndrome (XLP). This rare disease is often associated with diverse natural killer (NK)‐, B‐ and T‐cell deficiencies. We describe experiments testing whether the B lymphocytes of affected males play a role in the pathogenesis of XLP due to a low susceptibility to T‐cell‐mediated immunity. Using reverse transcription‐polymerase chain 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‐2A, which provide targets for cytotoxic T cells. Major histocompatibility complex (MHC) class I, MHC class II and the B7 costimulatory molecule were present on the cell surface. Accordingly, the EBV‐infected B cells were lysed in 51 Cr‐release assays by T lymphocytes sharing MHC determinants with the targets. This MHC‐restricted and specific lysis was confirmed in competition experiments using MHC‐specific monoclonal antibodies (MAbs) and synthetic peptides. XLP‐derived LCLs could also induce MHC class I‐restricted memory and cytotoxic T lymphocytes. Thus, these XLP‐derived B cells resembled normal LCIs in vitro with respect to induction of EBV‐specific cytotoxic T cells (CTL), the ability to present EB viral antigens and the susceptibility to 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. Int. J. Cancer 76:694–701, 1998.© 1998 Wiley‐Liss, Inc.