Activation of human thymocytes after infection by EBV.
The discovery of EBV in certain T cell malignancies and the expression of the EBV receptor, CR2/CD21, on a population of immature thymocytes, T lymphoblastoid cell lines, and childhood acute T lymphoblastic leukemia cells suggested that EBV-receptor interactions on T cells may be of importance. We have shown that, within the thymus, a population of large, immature cells expresses CD21. EBV altered the activation responses of immature thymocytes in vitro. Triggering through CD2 is mitogenic for mature, but not immature, T cells. However, during infection by EBV, ligation of CD2 caused thymocytes to proliferate in the absence of exogenous cytokines. This function was a result of the interaction of EBV with its receptor, CD21, but was caused by infection rather than surface signaling, because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect of B95-8. Immature thymocytes were infected by EBV, as determined by the internalization of the viral genome and its transcriptional activity. Consistent with the activity of B95-8, EBNA-2 transcripts were identified within infected thymocyte populations. In addition, components of the viral replicative pathway were expressed during infection of thymocytes. These components included transcription of BZLF-1, an early gene that characterizes EBV-infected B cells after disruption of latency. A second transcript was identified as encoding the recently characterized RAZ, which also is associated with replicative infection. The consequences of EBV infection of T cells at an early stage of differentiation may lead to failure of normal T cell repertoire development, autoimmunity, or malignancy.
Paterson
R L
RL
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Kelleher
C A
CA
Streib
J E
JE
Amankonah
T D
TD
Xu
J W
JW
Jones
J F
JF
Gelfand
E W
EW
D000956:Antigens, Viral / Q000096:biosynthesis; D001483:Base Sequence; D015139:Blotting, Southern; D002478:Cells, Cultured; D002675:Child, Preschool; D004261:DNA Replication / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D019309:Epstein-Barr Virus Nuclear Antigens; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D017464:Receptors, Complement 3d / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D015534:Trans-Activators / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000276:immunology*; D014764:Viral Proteins / Q000096:biosynthesis
D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D017464:Receptors, Complement 3d; D015534:Trans-Activators; D014764:Viral Proteins