CTLA4Ig attenuates accelerated rejection (presensitization) in the mouse islet allograft model.
BACKGROUND
Sensitization to donor antigens is a problem of growing magnitude in clinical transplantation. At a molecular level, this is due to the interaction between antigen bearing antigen-presenting cells and recipient T cells and involves both antigen presentation and co-stimulation.


METHODS
Allogeneic islet transplantation was performed using DBA/2J donors and B6AF1 recipients. Four weeks before transplantation, recipient animals were given donor-specific transfusion (DST) alone, DST + CTLA4Ig, DST + control IgG, or no treatment. Graft loss was defined as a blood glucose >300 mg/100 ml.


RESULTS
Administration of DST + control IgG 4 weeks before transplantation resulted in accelerated rejection due to presensitization (median survival time of 8 days, compared with 14.5 days for the no-treatment group). Animals treated with CTLA4Ig in combination with DST had a median survival time of 12 days, compared with 8 days for DST + IgG.


CONCLUSIONS
CTLA4Ig attenuates the tempo of accelerated rejection in this islet allograft model of presensitization, but does not prolong allograft survival as compared with no treatment.
Roy-Chaudhury
P
P
Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Nickerson
P W
PW
Manfro
R C
RC
Zheng
X X
XX
Steiger
J
J
Li
Y S
YS
Strom
T B
TB
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D001803:Blood Transfusion; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D019172:Transplantation Conditioning
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept