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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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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
2007-06-28 14:06:23
date last changed
2017-01-01 06:42:50
@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},
  keyword      = {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.},
  volume       = {73},
  year         = {2002},
}