The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: A crosscheck hypothesis

Meng-Kun Tsai, Hong-Nerng Ho, Hsiung-Fei Chien, Pu Ou-Yang, Chun-Jean Lee, Po-Huang Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. Methods. A low-responding cardiac transplant model (BALB/c→B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. Results. B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. Conclusions. Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.
Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalTransplantation
Volume77
Issue number1
DOIs
Publication statusPublished - 2004
Externally publishedYes

Keywords

  • antigen
  • B7 antigen
  • CD86 antigen
  • cytotoxic T lymphocyte antigen 4
  • interleukin 2
  • unclassified drug
  • allotransplantation
  • animal cell
  • animal experiment
  • animal model
  • antigen function
  • article
  • cell infiltration
  • cell proliferation
  • clinical pathway
  • controlled study
  • cytokine production
  • female
  • flow cytometry
  • heart transplantation
  • immunocytochemistry
  • immunological tolerance
  • long term care
  • mouse
  • nonhuman
  • priority journal
  • regulatory mechanism
  • signal transduction
  • spleen cell
  • Adoptive Transfer
  • Animals
  • Antigens, CD
  • Antigens, CD4
  • Antigens, CD80
  • Antigens, CD86
  • Antigens, Differentiation
  • Cell Division
  • Concanavalin A
  • Female
  • Graft Survival
  • Heart Transplantation
  • Interleukin-2
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred Strains
  • Models, Immunological
  • Monocytes
  • Myocardium
  • Receptors, Interleukin-2
  • Spleen
  • Time Factors
  • Transplantation Tolerance
  • Transplantation, Homologous

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