1. ¹Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
2. ²Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA
3. ³Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
4. ⁴Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

Correspondence: Dr H Goldstein, Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA. E-mail: hgoldste@aecom.yu.edu

Received 27 May 2008; Revised 15 August 2008; Accepted 9 September 2008; Published online 25 December 2008.

Abstract

The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with -cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted -cells from an alloimmune attack. The insulin-producing -cell line TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID/. The efficiency of lentiviral transduction of TC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I major histocompatibility complex expression by over 90%, whereas RID/ expression inhibited cytokine-induced Fas upregulation by over 75%. TC-tet cells transduced with gp19K and RID/ lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c severe combined immunodeficient mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of -cells using gp19K- and RID/-expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents necessary at present for prolonged engraftment with transplanted islets.