Interleukin-2-diphtheria toxin fusion protein prolongs murine islet cell engraftment.
Allograft rejection is dependent upon complex cell-mediated processes, the primary effectors of which are activated T cells. As the expression of the cell surface protein interleukin 2 receptor is primarily limited to the subset of stimulated T cells, therapeutic agents that target this molecule may provide highly selective immunosuppression. A newly constructed chimeric IL-2 diphtheria toxin fusion protein specifically binds to and poisons activated T cells bearing the high-affinity IL-2R. We describe the in vivo effects of IL-2 toxin in preventing rejection of a crude pancreatic islet preparation transplanted across major and minor histoincompatibility barriers. IL-2 toxin administered once daily as the sole immunosuppressive agent prolongs islet graft survival and decreases the severity of the early mononuclear cell infiltrate into the graft site. Long-term survival of transplanted islets (greater than 100 days) was achieved following a short course (10 days) of more-intensive IL-2 toxin treatment. Thus IL-2 toxin, a highly selective immunosuppressive agent, leads to prolonged islet cell engraftment while sparing the resting or memory subset of the entire T cell repertoire.
Pankewycz
O
O
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Boston, MA 02115.
Mackie
J
J
Hassarjian
R
R
Murphy
J R
JR
Strom
T B
TB
Kelley
V E
VE
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000601:surgery; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*
D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins