Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2012 Feb 17;148(4):739-51. doi: 10.1016/j.cell.2011.12.031.

Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model.

Author information

  • 1Program of Cellular and Molecular Medicine, Children's Hospital and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.

Abstract

B cells infected by Epstein-Barr virus (EBV), a transforming virus endemic in humans, are rapidly cleared by the immune system, but some cells harboring the virus persist for life. Under conditions of immunosuppression, EBV can spread from these cells and cause life-threatening pathologies. We have generated mice expressing the transforming EBV latent membrane protein 1 (LMP1), mimicking a constitutively active CD40 coreceptor, specifically in B cells. Like human EBV-infected cells, LMP1+ B cells were efficiently eliminated by T cells, and breaking immune surveillance resulted in rapid, fatal lymphoproliferation and lymphomagenesis. The lymphoma cells expressed ligands for a natural killer (NK) cell receptor, NKG2D, and could be targeted by an NKG2D-Fc fusion protein. These experiments indicate a central role for LMP1 in the surveillance and transformation of EBV-infected B cells in vivo, establish a preclinical model for B cell lymphomagenesis in immunosuppressed patients, and validate a new therapeutic approach.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22341446
[PubMed - indexed for MEDLINE]
PMCID:
PMC3313622
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk