Cell membrane modification for rapid display of proteins as a novel means of immunomodulation: FasL-decorated cells prevent islet graft rejection.
Long-term display of exogenous proteins on the cell surface may have important research and therapeutic implications. We report a novel method for the cell-surface display of proteins that involves generation of a chimeric protein with core streptavidin, biotinylation of cells, and "decoration" with the protein. A chimeric protein with the extracellular portions of FasL (SA-FasL) was efficiently displayed on the cell surface within 2 hr without detectable cellular toxicity. Biotin and SA-FasL persisted on the cell surface for weeks in vitro and in vivo. Immunomodulation with SA-FasL-decorated splenocytes effectively blocked alloreactive responses in naive and presensitized rodents and prevented the rejection of allogeneic pancreatic islets. This approach may serve as an alternative to gene transfer-based expression with broad research and therapeutic applications.
Yolcu
Esma S
ES
Institute for Cellular Therapeutics and Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA.
Askenasy
Nadir
N
Singh
Narendra P
NP
Cherradi
Salah-Eddine Lamhamedi
SE
Shirwan
Haval
H
D000818:Animals; D016525:Antigenic Modulation / Q000235:genetics / Q000276:immunology*; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins