Multiple negative feedbacks on CD152 expression in allograft tolerance

Meng-Kun Tsai, Hong-Nerng Ho, Hsiung-Fei Chien, Mei-Ching Tzeng, Chien-Hsing Chen, Po-Huang Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background. CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. Methods. A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. Results. B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. Conclusions. CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.
Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalTransplantation
Volume79
Issue number2
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • CD152
  • CD80
  • CD86
  • Transplant tolerance
  • B7 antigen
  • B7 monoclonal antibody
  • CD86 antigen
  • cytotoxic T lymphocyte antigen 4
  • lymphocyte antigen
  • messenger RNA
  • monoclonal antibody
  • monoclonal antibody cd152
  • monoclonal antibody CD28
  • monoclonal antibody CD80
  • monoclonal antibody cd86
  • unclassified drug
  • animal cell
  • animal experiment
  • antigen expression
  • article
  • controlled study
  • female
  • flow cytometry
  • fluorescence microscopy
  • heart graft
  • heart transplantation
  • lymphocyte proliferation
  • mouse
  • mouse strain
  • negative feedback
  • nonhuman
  • organ donor
  • priority journal
  • real time polymerase chain reaction
  • recipient
  • RNA transcription
  • spleen cell
  • T lymphocyte
  • transplantation tolerance
  • Animals
  • Antigens, CD
  • Antigens, CD80
  • Antigens, CD86
  • Antigens, Differentiation
  • Cell Division
  • DNA Primers
  • Female
  • Heart Transplantation
  • Immune Tolerance
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen
  • T-Lymphocytes
  • Transcription, Genetic
  • Transplantation, Homologous

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