Inhibition of Apoptosis by Expression of Antiapoptotic Proteins in Recombinant Human Keratinocytes

Cell Transplantation

Article

Yeong-Hoon Choi¹  Peter M. Vogt²  Claudia Y. U. Choi²  Susanne Kall²  Kerstin Reimers²  Christina Allmeling² 

[1] Department of Cardiac Surgery, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA;Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover, D-30625 Hannover, Germany;

关键词: Apoptosis;    Keratinocytes;    Allotransplantation;    Inhibition of rejection;   

DOI  :  10.3727/000000007783465037

 received in 2006-10-06, accepted in 2006-12-07,  发布年份 2007

来源: Sage Journals

【 摘 要 】

The Fas ligand/Fas interaction plays an important role in the regulation of immune responses. Allografted cells undergo Fas-mediated apoptosis induced by CD8+ T cells. Our objective was to prevent human keratinocytes from immunologically induced apoptosis. We focused on three proteins with inhibitory function on Fas-mediated apoptosis. Human keratinocytes were transfected with either Flip, Faim, or Lifeguard (LFG). The treatment proved to be practicable and efficient. The recombinant keratinocytes with expression of our target proteins were cocultured with CD8+ T cells and the apoptotic activity was then evaluated. Activation of caspase-8 was detectable in control but not in the recombinant cells. Quantitative analysis revealed significant induction of T-cell-induced apoptosis in nontransfected keratinocytes (p = 0.04, n = 12) but not in Flip (p = 0.66), Faim (p = 0.42), or LFG (p = 0.44) expressing cells. Our results suggest that heterotopic expression of antiapoptotic proteins can induce the resistance of keratinocytes to a major mechanism of rejection.

【 授权许可】

Unknown   
© 2007 Cognizant Comm. Corp.