Increased number of Epstein-Barr virus latently infected B-cells in T-cell non-Hodgkin's lymphoma tissues

Abstract

Epstein-Barr virus (EBV) is a causative agent of malignant lymphomas occurring in immunocompromised hosts. Similar lymphoid tumors can be induced in mice with severe combined immunodeficiency (SCID mice) by transplanting human B-cells with latently infected EBV. We have previously observed that when apparently EBV-negative lymphomas were engrafted into SCID mice, 11 of 18 T-cell non-Hodgkin's lymphomas (NHLs) produced EBV associated lymphomas, but only 2 of 30 engrafted with B-NHLs. Previous studies suggested that EBV-infected cell inducing lymphomas in SCID mice may preferentially exist in T-cell NHL tissues. To prove this assumption, in situ hybridization (ISH) using oligonucleotide probes for EBV-encoded small RNAs 1 (EBER1) was used in this study to demonstrate EBV-bearing lymphocytes in NHL tissues. It was found that EBV-bearing cells existe in 9 of the 10 T-cell NHL surgical specimens. By contrast, in B cell NHLs, only 2 of 10 carried EBV-bearing cells. Further semi-quantitative analysis demonstrated that apparently significantly more EBV-bearing cells were present in T-cell NHL tissues than in B-cell NHLs. Moreover, these EBV-bearing cells in lymphoma tissues were shown to be of B-cell lineage, by the combinated analysis of immunostaining with CD20 and ISH with EBER1. These results indicated the increase of EBV-bearing B-cells in T-cell NHL tissues, suggesting the activation of B-cells with latently infected EBV by neoplastic T-cells.