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. 1988 Jun 1;167(6):1811–1824. doi: 10.1084/jem.167.6.1811

Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein- Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance

PMCID: PMC2189677  PMID: 2898508

Abstract

Some EBV+ BL cell lines continue to grow as single cells on in vitro passage, show an unusually restricted expression of EBV-latent genes and retain a BL biopsy-like cell surface phenotype (group I/II lines); others change to growth in aggregates, show a broader pattern of virus latent gene expression, and develop a cell surface phenotype more characteristic of EBV-transformed LCL (group III lines). Here we show that the cell surface adhesion molecules LFA-1, ICAM-1, and LFA-3 are expressed at very low levels, if at all, on group I/II lines and are coordinately upregulated as BL lines move towards group III. The change to growth in aggregates reflects the increasing availability of LFA-1 and ICAM-1, the two ligands whose mutual interaction underlies homotypic BL cell adhesion in vitro. The low levels of ICAM-1 and LFA-3 on group I/II BL cell lines are also associated with an impaired ability to interact with EBV-specific CTL in the antigen-independent phase of effector/target conjugation. mAb blocking studies show that the small number of conjugates that are formed with group I/II BL targets involve the LFA-1/ICAM-1 adhesion pathway but not the LFA-3 pathway; in contrast, both pathways contribute to the efficient conjugate formation shown by group III BL or LCL targets. Earlier work identified one group III line, WW1 BL, as unusual since is expressed the full spectrum of EBV-latent proteins yet remained insensitive to lysis by EBV-specific CTL. Here we show that this line has an anomalous pattern of adhesion molecule expression with high levels of LFA-1 and ICAM-1 in the absence of detectable LFA-3. The WW1 BL cells form conjugates with EBV-specific CTL through the LFA-1/ICAM-1 pathway, but in the absence of a target LFA-3/effector CD2 interaction these conjugates do not achieve target cell lysis. This may reflect an important role for target LFA-3 molecules in activating EBV-specific CTL function. From these in vitro studies, we postulate that downregulation of the adhesion molecules LFA-3 and ICAM-1 on EBV+ BL underlies the ability of the malignant clone to evade EBV-specific T cell surveillance in vivo.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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