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. 2002 Dec;123(6):1877-88.
doi: 10.1053/gast.2002.37066.

Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer

Catherine Van Montfrans  1 , Erik Hooijberg, Maria Sol Rodriguez Pena, Esther C De Jong, Hergen Spits, Anje A Te Velde, Sander J H Van Deventer
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Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer

Catherine Van Montfrans et al. Gastroenterology. 2002 Dec.

Abstract

Background & aims: Systemic treatment of Crohn's disease patients using recombinant interleukin (rIL)-10 has not resulted in significant therapeutic benefit presumably because of limited bioavailability and unexpected proinflammatory effects of high-dose rIL-10. Ex vivo gene transfer of the interleukin (IL)-10 gene to gut-homing CD4(+) cells may lead to improved long-term management.

Methods: Peripheral blood mononuclear cells (PBMCs) were transduced with a retroviral vector containing the IL-10 and green fluorescent protein (GFP) gene or a control vector containing GFP only. Transduced CD4(+) cells were sorted and maintained in culture for phenotypic and functional analysis.

Results: Stimulated IL-10-GFP CD4(+) cells produced significantly higher levels of IL-10 than control cells for at least 4 months. The IL-10 transgene was biologically active and decreased proliferation of IL-10-GFP CD4(+) cells as well as expression of major histocompatibility class (MHC) class II, proliferation of autologous responder cells, and IL-12 production by dendritic cells (DCs). The majority of transduced CD4(+) cells had a gut-homing potential because they expressed the mucosal integrin alpha4beta7, and displayed efficient binding to MAdCAM-1-expressing cells in vitro.

Conclusions: Transduction of peripheral blood CD4(+) lymphocytes with IL-10 results in a regulatory phenotype. The use of regulatory gut-homing human CD4(+) cells may provide a novel approach to local delivery of immunomodulatory signals to the intestine in Crohn's disease.

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