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Effect of Triple Costimulation Blockade on Islet Allograft Survival in Sensitized Mice

Diab, R.; Iwata, T.; Corbascio, M.; Tibell, A.; Ekberg, Henrik LU ; Holgersson, J. and Kumagai-Braesch, M. (2010) Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association In Transplantation Proceedings 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:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
in
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
external identifiers
  • wos:000280953400030
  • scopus:77955539951
ISSN
0041-1345
1873-2623
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
2010-09-23 11:04:15
date last changed
2018-05-29 11:13:27
@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         = {0041-1345},
  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},
  volume       = {42},
  year         = {2010},
}