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.
CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival / F. D'Addio, T. Ueno, M. Clarkson, B. Zhu, A. Vergani, G.J. Freeman, M.H. Sayegh, M.J.I. Ansari, P. Fiorina, A. Habicht. - In: PLOS ONE. - ISSN 1932-6203. - 8:4(2013 Apr 04).
|Titolo:||CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival|
D'ADDIO, FRANCESCA (Primo)
FIORINA, PAOLO (Penultimo)
|Parole Chiave:||animals; antigen-presenting cells; antigens, cd; antigens, cd28; antigens, cd4; cytokines; cytotoxicity, immunologic; gpi-linked proteins; gene expression; graft survival; heart transplantation; histocompatibility antigens class i; immunoglobulin g; immunologic memory; interferon-gamma; killer cells, natural; lymphocyte activation; mice; mice, inbred balb c; mice, inbred c57bl; mice, knockout; receptors, immunologic; recombinant fusion proteins; signal transduction; skin transplantation; t-lymphocyte subsets; transplantation, homologous; agricultural and biological sciences (all); biochemistry, genetics and molecular biology (all); medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||4-apr-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0060391|
|Appare nelle tipologie:||01 - Articolo su periodico|