No abstract

IntroductionThe human ␥-herpesvirus Epstein Barr virus (EBV) infects more than 90% of the adult population. Latent infection by EBV is associated with human cancers of epithelial and B-cell origin, including 95% of nasopharyngeal carcinoma 1 and 90% of endemic Burkitt lymphoma, and it is associated with 40% to 60% of Hodgkin lymphoma cases. 2 Although all latently infected B cells have the potential for malignant transformation, most carriers remain free of tumors due to an effective immune control of the virus. This becomes apparent in conditions of immune suppression. Increased frequencies of EBV-associated malignancies can be observed during immunosuppressive therapy 3 in patients with hereditary immunodeficiencies 4,5 or with immunocompromising coinfections like HIV-induced AIDS. 6 T cells are an essential part of EBV-specific immune control. This is evident from the successful treatment of posttransplantation lymphoproliferative disease (PTLD) with the adoptive transfer of EBV-specific T cells. 7,8 This study focuses on the CD4 ϩ T-cell response of healthy virus carriers to the latent EBV antigen Epstein-Barr nuclear antigen 1 (EBNA1), which is expressed in all EBV-associated malignancies. Maintenance of EBNA1 expression is due to its crucial function in viral persistence within proliferating cells. EBV DNA only rarely integrates into the host-cell genome 9 and is carried as circular DNA episome by most latently EBVinfected cells. 10,11 The EBNA1 protein initiates replication of viral episomes prior to mitosis and anchors viral DNA to mitotic chromosomes during cell division. 12 By this mechanism, EBV replicates in proliferating cells without viral particle formation during latent EBV infection.EBNA1 should be a critical target of protective immunity because it is expressed in all EBV-positive proliferating cells and is crucial for viral persistence. However, earlier studies have emphasized escape of EBNA1 from CD8 ϩ T-cell detection due to an amino terminal gly-ala repeat domain. [13][14][15] Since it is consistently recognized by CD4 ϩ T cells in healthy EBV carriers, 16,17 it was appreciated that EBNA1 is a promising T-cell antigen to target EBV-transformed B cells. 18 EBNA1-specific effector CD4 ϩ T cells are primarily T-helper 1 (TH1) polarized, 19 can target EBVtransformed B cells, 16,[19][20][21] and prevent EBV-mediated B-cell transformation in vitro. 22 EBNA1-specific CD4 ϩ T cells can also mediate rejection of EBNA1-positive Burkitt lymphoma transplanted into mice. 23 Recently, EBNA1-specific CD8 ϩ T cells, in association with a few HLA class I haplotypes, have also been reported to recognize EBV-transformed B cells [24][25][26] and to prevent their outgrowth in vitro. 25 Therefore, both EBNA1-specific CD4 ϩ and CD8 ϩ T cells are able to recognize EBV-transformed cells and deserve to be studied in more detail.In this study, we characterized EBNA1-specific CD4 ϩ T cells in healthy EBV carriers by flow cytometry-based intracellular cytokine staining and proliferation assays, using an overlapping pep...

Anthracyclines result in early and persistent abnormalities in 3D mechanics. The 3D LVEF and strain measures are associated with concurrent and subsequent systolic dysfunction, and concurrent diastolic dysfunction. Future research is needed to define the mechanisms and clinical relevance of abnormal 3D mechanics.

Circumcision does not appear to have adverse, clinically important effects on male sexual function in sexually active adults who undergo the procedure.