Costimulation Blockade-Induced Cardiac Allograft Tolerance: Inhibition of T Cell Expansion and Accumulation of Intragraft cD4+Foxp3+ T Cells.
(2006) In Transplantation 82(11). p.1493-1500- Abstract
- Background. Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1. Methods. Recombinase activating gene-deficient (Rag1(-/-)) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or... (More)
- Background. Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1. Methods. Recombinase activating gene-deficient (Rag1(-/-)) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-)CD103(-) T cells and treated with costimulation blockade. Intragraft T cells from C57BL/6 recipients were analyzed for the expression of the Foxp3 protein after tolerance induction. Results. Mice reconstituted with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-) CD103(-) T cells and treated with costimulation blockade accepted allografts permanently. Analysis of cells from recipient mice adoptively transferred with CD4(+)CD25(-) T cells contained a population of CD4(low)CD25(+) T cells 100 days after transplantation. Costimulation blockade partially prevented the homeostatic proliferation of CD4(+)CD25(-)CD103(-) T cells in Rag-1(-/-) recipients. Accepted allografts contained an elevated number of CD4(+)Foxp3(+) T cells. Conclusions. These results indicate that T-cell derived IL-10 is not essential for induction of graft acceptance in mice treated with costimulation blockade, but that treatment limits T-cell expansion in the recipients. The results further indicate that tolerance is maintained by intragraft CD4(+)Foxp3(+) T cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/164040
- author
- Oderup, Cecilia LU ; Malm, Helene LU ; Ekberg, Henrik LU ; Qi, Zhongquan LU ; Veress, Bela LU ; Ivars, Fredrik LU and Corbascio, Matthias
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Foxp3, regulatory T cell, heart transplantation, costimulation blockade, tolerance
- in
- Transplantation
- volume
- 82
- issue
- 11
- pages
- 1493 - 1500
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000242948600020
- scopus:33845703869
- ISSN
- 1534-6080
- DOI
- 10.1097/01.tp.0000244064.66136.04
- language
- English
- LU publication?
- yes
- id
- 42a9d63d-c34d-4f7d-9966-7b0f1075256f (old id 164040)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17164722&dopt=Abstract
- date added to LUP
- 2016-04-01 15:43:50
- date last changed
- 2022-01-28 06:49:24
@article{42a9d63d-c34d-4f7d-9966-7b0f1075256f,
abstract = {{Background. Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1. Methods. Recombinase activating gene-deficient (Rag1(-/-)) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-)CD103(-) T cells and treated with costimulation blockade. Intragraft T cells from C57BL/6 recipients were analyzed for the expression of the Foxp3 protein after tolerance induction. Results. Mice reconstituted with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-) CD103(-) T cells and treated with costimulation blockade accepted allografts permanently. Analysis of cells from recipient mice adoptively transferred with CD4(+)CD25(-) T cells contained a population of CD4(low)CD25(+) T cells 100 days after transplantation. Costimulation blockade partially prevented the homeostatic proliferation of CD4(+)CD25(-)CD103(-) T cells in Rag-1(-/-) recipients. Accepted allografts contained an elevated number of CD4(+)Foxp3(+) T cells. Conclusions. These results indicate that T-cell derived IL-10 is not essential for induction of graft acceptance in mice treated with costimulation blockade, but that treatment limits T-cell expansion in the recipients. The results further indicate that tolerance is maintained by intragraft CD4(+)Foxp3(+) T cells.}},
author = {{Oderup, Cecilia and Malm, Helene and Ekberg, Henrik and Qi, Zhongquan and Veress, Bela and Ivars, Fredrik and Corbascio, Matthias}},
issn = {{1534-6080}},
keywords = {{Foxp3; regulatory T cell; heart transplantation; costimulation blockade; tolerance}},
language = {{eng}},
number = {{11}},
pages = {{1493--1500}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Transplantation}},
title = {{Costimulation Blockade-Induced Cardiac Allograft Tolerance: Inhibition of T Cell Expansion and Accumulation of Intragraft cD4+Foxp3+ T Cells.}},
url = {{http://dx.doi.org/10.1097/01.tp.0000244064.66136.04}},
doi = {{10.1097/01.tp.0000244064.66136.04}},
volume = {{82}},
year = {{2006}},
}