Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates.
Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.
Weaver
Tim A
TA
Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, US National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Charafeddine
Ali H
AH
Agarwal
Avinash
A
Turner
Alexandra P
AP
Russell
Maria
M
Leopardi
Frank V
FV
Kampen
Robert L
RL
Stempora
Linda
L
Song
Mingqing
M
Larsen
Christian P
CP
Kirk
Allan D
AD
D000069594:Abatacept; D000077944:Alefacept; D000818:Animals; D001803:Blood Transfusion; D018801:CD2 Antigens / Q000032:analysis; D006085:Graft Survival / Q000187:drug effects*; D018796:Immunoconjugates / Q000494:pharmacology; D007156:Immunologic Memory; D016030:Kidney Transplantation; D008253:Macaca mulatta; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D018801:CD2 Antigens; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D000069594:Abatacept; D000077944:Alefacept; D020123:Sirolimus