Epstein-Barr virus (EBV) infection in B-cell non-Hodgkin's lymphomas in children: virus latency and its correlation with CD21 and CD23 molecules

Epstein Barr virus (EBV) infection of human B lymphocytes in vitro results in immortalisation of the cells and augmented membranous expression of numerous B-cell activation molecules, including CD23. Other studies demonstrated that only those B lymphocytes which carry the surface CD21 (EBV receptor) become transformation-competent. Inspired by the relatively unclear relations between expression of EBV and those of CD21 and CD23 in in vivo conditions we have decided to define correlations between tissue markers of EBV and of CD21 and CD23 molecules in B-cell non-Hodgkin's lymphomas (NHLs) in children. The studies were performed on an archival tissue material originating from children with B-cell NHLs (n=26) using immunocytochemical techniques, in situ hybridisation, and PCR. Our studies confirmed the latent phase of EBV infection in all of the EBV-positive patients. Viral proteins as well as viral RNAs (EBERs) was found both in the cytoplasm, in cell nuclei and in cell membranes of mainly the transformed lymphocytes B. Expression of the latent proteins (EBNA2 and LMP1) and that of EBERs in B-cell NHLs was significantly higher as compared to children with nonneoplastic lesions. The studies demonstrated reciprocally positive correlations between expressions of CD21 and CD23 in our children, but no correlation could be demonstrated between expression of EBV tissue markers and that of CD21 and/or CD23. Positive correlation was confirmed between expression of EBNA2 and LMP1 as well as between expression of the two proteins and EBERs in B-cell NHLs. Our studies have shown mainly latency III pattern of EBV. We have also demonstrated a novel form of EBV latency with no EBERs expression. The high detectability of EBV-positive cases both in the group of B-cell NHLs (77%), and in the group with non-neoplastic lesions (64%) suggested that only more pronounced tissue expression of EBV markers in B-cell NHLs as compared to the non-neoplastic material may point to a potential role of EBV in pathogenesis of lymphoma in this group of population in our country.     

Type 2 cytokines predominate in the human CD4(+) T-lymphocyte response to Epstein-Barr virus nuclear antigen 1

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persistently infects 85% of the adult population worldwide. In this report, we examine the proliferative response and cytokine secretion profile of CD4(+) T lymphocytes from a panel of unrelated EBV-positive donors against two EBV latent antigens, EBNA1 and EBNA3C. Substantial proliferative responses by CD4(+) lymphocytes were demonstrated to both antigens in multiple, randomly selected donors. Surprisingly, we observed a striking and consistent difference in cytokine response to EBNA1 and EBNA3C. EBNA1-specific CD4(+) T lymphocytes from multiple unrelated donors preferentially produced type 2-like cytokines in response to antigenic stimulation, while the response to EBNA3C was a characteristic type 1 response. The implications of these findings for EBV persistence and the development of EBV-associated malignancies are discussed.