Epstein-Barr Virus, B Cell Lymphoproliferative Disease, and SCID Mice: Modeling T Cell Immunotherapy In Vivo

被引:5
作者
Johannessen, I. [1 ]
Bieleski, L. [1 ]
Urquhart, G. [1 ]
Watson, S. L. [1 ]
Wingate, P. [1 ]
Haque, T. [1 ]
Crawford, D. H. [1 ]
机构
[1] Univ Edinburgh, Ctr Infect Dis, Edinburgh, Midlothian, Scotland
基金
英国惠康基金;
关键词
Epstein-Barr virus; B cell lymphoma; immunotherapy; SCID mouse; SEVERE COMBINED IMMUNODEFICIENCY; SCID/SCID MICE; LYMPHOCYTES; EBV; LYMPHOMA; IDENTIFICATION; ANTIGENS; THERAPY; HOMEOSTASIS; GENERATION;
D O I
10.1002/jmv.22164
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) arises in up to 10% of organ transplant recipients and is fatal in similar to 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 out-growth 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. J. Med. Virol. 83: 1585-1596, 2011. (C) 2011 Wiley-Liss, Inc.
引用
收藏
页码:1585 / 1596
页数:12
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