EPSTEIN-BARR VIRUS, B CELL LYMPHOPROLIFERATIVE DISEASE, T CELL IMMUNOTHERAPY AND SCID MOUSE MODELLING

Ingolfur Johannessen (1) , Lara Bieleski (1) , Gillian Urquhart (1) , Sarah Watson (1) , Phoebe Wingate (1) , Tanzina Haque (2) , Dorothy Crawford (3)

1 Centre for Infectious Diseases
2 Centre for Virology
3 CLINICAL AND MOLECULAR VIROLOGY

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) arises in up to 10% of organ transplant recipients and is fatal in ~50% of cases. PTLD can be modelled in SCID mice using EBV+ve human B lymphoblastoid cell lines (BLCLs), and the current study investigated intraperitoneal (ip) inoculation of such animals in experiments which assessed the effect of EBV-specific cytotoxic T lymphocytes (CTLs) and cytokines on PTLD growth. Ip transfer of 1 dose of autologous CTLs, or CD8-enriched T cells, into ip BLCL-inoculated animals significantly delayed tumour development (p=0.001) and prevented tumour formation in a significant proportion (40%) of mice (p=0.001). A combination of IL2, 7 and 15 conditioning of CTLs prior to ip injection significantly delayed ip BLCL-derived tumour formation in vivo when compared to CTLs expanded in vitro using only IL2 (p=0.04) and prevented tumour outgrowth in a significant proportion (60%) of mice (p=0.02). Daily ip IL2 dosing of ip CTL-inoculated mice significantly delayed tumour development in vivo (p=0.004) and prevented tumour outgrowth in a significant proportion (78%) of mice (p=0.02) when compared to animals dosed with vehicle only. In SCID mice, autologous CTLs, and CD8-enriched T cells, have significant capacity to hinder development of PTLD-like tumours. Whilst studies are needed to delineate the role of cytokine conditioning and CD4-enriched T cells, the results suggest that IL2 plays a key role in supporting CTL funtion in vivo.

Mots clés: Medicine

Ingolfur Johannessen, Lara Bieleski, Gillian Urquhart, Sarah Watson, Phoebe Wingate, et al.. EPSTEIN-BARR VIRUS, B CELL LYMPHOPROLIFERATIVE DISEASE, T CELL IMMUNOTHERAPY AND SCID MOUSE MODELLING. Journal of Medical Virology, 2011, 83 (9), pp.1585. ⟨10.1002/jmv.22164⟩. ⟨hal-00657569⟩