Effect of triple costimulation blockade on islet allograft survival in sensitized mice.

Abstract

BACKGROUND:

Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice.

METHODS:

C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8.

RESULTS:

Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10).

CONCLUSION:

Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.

• Authors: R Diab, T Iwata, M Corbascio, A Tibell, H Ekberg, J Holgersson, M Kumagai-Braesch
• Journal: Transplantation proceedings (Transplant Proc) 2010 Jul-Aug Vol. 42 Issue 6 Pg. 2109-11 ISSN: 1873-2623 [Electronic] United States
• PMID: 20692420 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Blood Glucose
• CTLA-4 Antigen
• Ctla4 protein, mouse
• Immunoglobulin G

Topics

• Animals
• Antigens, CD (immunology)
• Blood Glucose (metabolism)
• CTLA-4 Antigen
• Diabetes Mellitus, Experimental (blood, surgery)
• Graft Rejection (blood)
• Graft Survival (physiology)
• Immunoglobulin G (immunology)
• Islets of Langerhans Transplantation (immunology, pathology, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Reoperation
• Transplantation, Homologous (immunology, pathology, physiology)