title: Epstein-Barr virus, B cell lymphoproliferative disease, and SCID mice: modeling T cell immunotherapy in vivo.
abstract: 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 modeled 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 one dose of autologous CTLs, or CD8-enriched T cells, into ip BLCL-inoculated animals significantly delayed tumor development (P = 0.001) and prevented tumor formation in a significant proportion (40%) of mice (P = 0.001). A combination of interleukin (IL)2, 7, and 15 conditioning of CTLs prior to ip injection significantly delayed ip BLCL-derived tumor formation in vivo when compared to CTLs expanded in vitro using only IL2 (P = 0.04) and prevented tumor outgrowth in a significant proportion (60%) of mice (P = 0.02). Daily ip IL2 dosing of ip CTL-inoculated mice significantly delayed tumor development in vivo (P = 0.004) and prevented tumor 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 tumors. 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.
authors: Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh United Kingdom. i.johannessen@ed.ac.uk
authors: I
authors: I
authors: Johannessen
authors: L
authors: L
authors: Bieleski
authors: G
authors: G
authors: Urquhart
authors: S L
authors: SL
authors: Watson
authors: P
authors: P
authors: Wingate
authors: T
authors: T
authors: Haque
authors: D H
authors: DH
authors: Crawford
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000628:therapy*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D007167:Immunotherapy; D017403:In Situ Hybridization; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation* / Q000821:virology
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7