Anti-LFA-1 Improves Pig Islet Xenograft Function in Diabetic Mice When Long-Term Acceptance Is Induced by CTLA4Ig/Anti-CD40L.
(2007) In Transplantation 83(9). p.1259-1267- Abstract
- Background. It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C5713L/6 mice with streptozotocin-induced diabetes. Methods. Recipients were treated with CTLA4Ig/anti-CD40L +/- anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. Results. Recipients treated with... (More)
- Background. It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C5713L/6 mice with streptozotocin-induced diabetes. Methods. Recipients were treated with CTLA4Ig/anti-CD40L +/- anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. Results. Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L-treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti-CD40L +/- anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas control antibody-treated mice did. CD4+ T cells from costimulation blockade-treated recipients proliferated less than CD4+ T cells from control antibody-treated mice when co-cultured with syngeneic antigen presenting cells loaded with pig islet antigens. Conclusions. CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients. However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/168328
- author
- Kumagai-Braesch, Makiko ; Ekberg, Henrik LU ; Wang, Feng ; Osterholm, Cecilia ; Ehrnfelt, Cecilia ; Sharma, Amit ; Lindeborg, Ellinor ; Holgersson, Jan and Corbascio, Matthias
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CTLA4Ig, anti-CD40L, anti-LFA-1, pig islet transplantation, costimulatory blockade
- in
- Transplantation
- volume
- 83
- issue
- 9
- pages
- 1259 - 1267
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000246668500019
- scopus:34248332137
- ISSN
- 1534-6080
- DOI
- 10.1097/01.tp.0000261722.02697.75
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Renal Research Unit (013242210), Emergency medicine/Medicine/Surgery (013240200)
- id
- c878ca45-3c35-4ba8-9246-80e63dbdb637 (old id 168328)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17496544&dopt=Abstract
- date added to LUP
- 2016-04-01 17:04:45
- date last changed
- 2025-04-04 14:56:34
@article{c878ca45-3c35-4ba8-9246-80e63dbdb637,
abstract = {{Background. It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C5713L/6 mice with streptozotocin-induced diabetes. Methods. Recipients were treated with CTLA4Ig/anti-CD40L +/- anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. Results. Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L-treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti-CD40L +/- anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas control antibody-treated mice did. CD4+ T cells from costimulation blockade-treated recipients proliferated less than CD4+ T cells from control antibody-treated mice when co-cultured with syngeneic antigen presenting cells loaded with pig islet antigens. Conclusions. CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients. However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment.}},
author = {{Kumagai-Braesch, Makiko and Ekberg, Henrik and Wang, Feng and Osterholm, Cecilia and Ehrnfelt, Cecilia and Sharma, Amit and Lindeborg, Ellinor and Holgersson, Jan and Corbascio, Matthias}},
issn = {{1534-6080}},
keywords = {{CTLA4Ig; anti-CD40L; anti-LFA-1; pig islet transplantation; costimulatory blockade}},
language = {{eng}},
number = {{9}},
pages = {{1259--1267}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Transplantation}},
title = {{Anti-LFA-1 Improves Pig Islet Xenograft Function in Diabetic Mice When Long-Term Acceptance Is Induced by CTLA4Ig/Anti-CD40L.}},
url = {{http://dx.doi.org/10.1097/01.tp.0000261722.02697.75}},
doi = {{10.1097/01.tp.0000261722.02697.75}},
volume = {{83}},
year = {{2007}},
}