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CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.

Malm, Helene ; Corbascio, Matthias ; Österholm, Cecilia LU ; Cowan, Shannon ; Larsen, Christian P ; Pearson, Thomas C and Ekberg, Henrik LU (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)
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published
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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}},
}