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Epstein‐Barr virus, B cell lymphoproliferative disease, and SCID mice: Modeling T cell immunotherapy in vivo
Author(s) -
Johannessen I.,
Bieleski L.,
Urquhart G.,
Watson S.L.,
Wingate P.,
Haque T.,
Crawford D.H.
Publication year - 2011
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.22164
Subject(s) - in vivo , cytotoxic t cell , cd8 , immunotherapy , immunology , cytokine , ctl* , adoptive cell transfer , interleukin 2 , medicine , t cell , transplantation , immune system , biology , in vitro , biochemistry , microbiology and biotechnology
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. J. Med. Virol. 83:1585–1596, 2011. © 2011 Wiley‐Liss, Inc.