Effect of Triple Costimulation Blockade on Islet Allograft Survival in Sensitized Mice
(2010) Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association 42(6). p.2109-2111- 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... (More)
- 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. Naive 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1673539
- author
- Diab, R. ; Iwata, T. ; Corbascio, M. ; Tibell, A. ; Ekberg, Henrik LU ; Holgersson, J. and Kumagai-Braesch, M.
- organization
- publishing date
- 2010
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- host publication
- Transplantation Proceedings
- volume
- 42
- issue
- 6
- pages
- 2109 - 2111
- publisher
- Elsevier
- conference name
- Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association
- conference location
- Venice, Italy
- conference dates
- 2009-10-12 - 2009-10-16
- external identifiers
-
- wos:000280953400030
- scopus:77955539951
- pmid:20692420
- ISSN
- 1873-2623
- 0041-1345
- DOI
- 10.1016/j.transproceed.2010.05.084
- language
- English
- LU publication?
- yes
- id
- 9bb6cda7-4815-433a-8b45-923545ae9193 (old id 1673539)
- date added to LUP
- 2016-04-01 11:07:13
- date last changed
- 2024-10-07 21:32:08
@inproceedings{9bb6cda7-4815-433a-8b45-923545ae9193,
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. Naive 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.}},
author = {{Diab, R. and Iwata, T. and Corbascio, M. and Tibell, A. and Ekberg, Henrik and Holgersson, J. and Kumagai-Braesch, M.}},
booktitle = {{Transplantation Proceedings}},
issn = {{1873-2623}},
language = {{eng}},
number = {{6}},
pages = {{2109--2111}},
publisher = {{Elsevier}},
title = {{Effect of Triple Costimulation Blockade on Islet Allograft Survival in Sensitized Mice}},
url = {{http://dx.doi.org/10.1016/j.transproceed.2010.05.084}},
doi = {{10.1016/j.transproceed.2010.05.084}},
volume = {{42}},
year = {{2010}},
}