CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.
(2002) In Transplantation 73(2). p.293-297- Abstract
- BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered... (More)
- BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/106259
- author
- Malm, Helene ; Corbascio, Matthias ; Österholm, Cecilia LU ; Cowan, Shannon ; Larsen, Christian P ; Pearson, Thomas C and Ekberg, Henrik LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Homologous, T-Lymphocytes/*immunology, Inbred BALB C, Mice, Inbred C3H, Inbred C57BL, Reoperation, Skin Transplantation/*immunology, Lymphocyte Transformation/*drug effects, Male, Immunosuppressive Agents/*pharmacology, Lymphocyte Function-Associated Antigen-1/*physiology, Transplantation, Graft Survival/*drug effects, Graft Rejection, Drug, Dose-Response Relationship, Antigens, Differentiation/*pharmacology, Animal
- in
- Transplantation
- volume
- 73
- issue
- 2
- pages
- 293 - 297
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:11821746
- wos:000173740800024
- scopus:0037180908
- ISSN
- 1534-6080
- language
- English
- LU publication?
- yes
- id
- 73f0e9bf-59ab-4024-aed8-cf4068839979 (old id 106259)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11821746&dopt=Abstract
- date added to LUP
- 2016-04-01 15:36:01
- date last changed
- 2022-01-28 06:05:43
@article{73f0e9bf-59ab-4024-aed8-cf4068839979,
abstract = {{BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.}},
author = {{Malm, Helene and Corbascio, Matthias and Österholm, Cecilia and Cowan, Shannon and Larsen, Christian P and Pearson, Thomas C and Ekberg, Henrik}},
issn = {{1534-6080}},
keywords = {{Homologous; T-Lymphocytes/*immunology; Inbred BALB C; Mice; Inbred C3H; Inbred C57BL; Reoperation; Skin Transplantation/*immunology; Lymphocyte Transformation/*drug effects; Male; Immunosuppressive Agents/*pharmacology; Lymphocyte Function-Associated Antigen-1/*physiology; Transplantation; Graft Survival/*drug effects; Graft Rejection; Drug; Dose-Response Relationship; Antigens; Differentiation/*pharmacology; Animal}},
language = {{eng}},
number = {{2}},
pages = {{293--297}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Transplantation}},
title = {{CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11821746&dopt=Abstract}},
volume = {{73}},
year = {{2002}},
}