Characterization of the expanded T cell population in infectious mononucleosis: apoptosis, expression of apoptosis-related genes, and Epstein-Barr virus (EBV) status.
Infectious mononucleosis (IM), a manifestation of primary infection with EBV, is characterized by a massive expansion of the T cell population. In this study we examined this expanded T cell population regarding its EBV status, its proliferative and apoptotic activity, and its expression of apoptosis-related genes. Whereas previous studies were performed on ex vivo cultures or on peripheral blood, our investigations included in vivo analysis of IM tonsillectomy specimens (14 cases) by in situ hybridization for viral RNA (EBERs) combined with immunohistochemistry (IHC; CD3, CD45RO, CD20, CD79a, Ki-67, Bcl-2, Bax, Fas, FasL) and the TUNEL method. Of the EBER+ cells 50-70% showed expression of the B cell markers CD20/CD79a. The remainder of the EBER+ cells expressed neither B nor T cell antigens. No co-expression of EBERs and T cell antigens was detected in any of the specimens. In accordance with a high rate of apoptosis (up to 2.37%) within the expanded T cell population, Bcl-2 expression was drastically reduced and FasL expression remarkably increased. The levels of Bax and Fas expression showed no or moderate up-regulation. In conclusion, the massive expansion of IM T cells is not caused by EBV infection of these cells but merely represents an intense immune reaction. Through altered expression of Bcl-2/Bax and Fas/FasL, the activated T cells are subject to enhanced apoptosis while residing within the lymphoid tissue, which eventually allows the efficient silencing of this potentially damaging T cell response.
Verbeke
C S
CS
Pathology Institute, Faculty of Clinical Medicine, University of Heidelberg, Heidelberg, Germany. Caroline.Verbeke@gw.sjsuh.northy.nhs.uk
Wenthe
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Bergler
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WF
Zentgraf
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D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis; D017209:Apoptosis; D017252:CD3 Complex / Q000096:biosynthesis; D051925:CD79 Antigens; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019394:Ki-67 Antigen / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis
D015703:Antigens, CD; D018951:Antigens, CD20; C494826:BAX protein, human; D017252:CD3 Complex; D051925:CD79 Antigens; C497881:CD79A protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D017493:Leukocyte Common Antigens