CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival

Francesca D'Addio, Takuya Ueno, Michael Clarkson, Baogong Zhu, Andrea Vergani, Gordon J. Freeman, Mohamed H. Sayegh, Mohammed Javeed I Ansari, Paolo Fiorina, Antje Habicht*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8+ cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig) we examined the role of the novel costimulatory molecule CD160 in mediating CD4+ or CD8+ T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8+ T cell proliferation and IFN-γ production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4-/-, CD28-/- knockout and CTLA4Ig treated WT recipients, but not in WT or CD8-/- knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8+ T cell proliferation, effector/memory responses and alloreactive IFN-γ production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8+ alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection.

Original languageEnglish (US)
Article numbere60391
JournalPloS one
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 4 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

D'Addio, F., Ueno, T., Clarkson, M., Zhu, B., Vergani, A., Freeman, G. J., ... Habicht, A. (2013). CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival. PloS one, 8(4), [e60391]. https://doi.org/10.1371/journal.pone.0060391