title: Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1.
abstract: Costimulatory and coinhibitory signals are important for the maintenance of immune homeostasis both in the steady state and during immune responses. In this study, we explore the relative contributions of these signals to the rapid production of large amounts of cytokines by activated invariant NKT cells (iNKT cells). We find that upon antigenic stimulation, iNKT cells rapidly up-regulate programmed death (PD)-1 and induce high levels of PD ligand 1 and costimulatory molecules on the surface of cognate Ag-presenting dendritic cells and that iNKT cells require a CD28 signal to secrete cytokines in the presence of a PD-1/PD ligand 1 interaction. CD28-deficient iNKT cells synthesized but failed to secrete cytokines during activation, and blockade of the PD-1 pathway restored the ability of CD28-deficient iNKT cells to secrete cytokines. The opposing functions of CD28 and PD-1 thus tightly regulate the unique effector function iNKT cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Zenebech
authors.initials: Z
authors.lastname: Wondimu
authors.forename: Mark
authors.initials: M
authors.lastname: Swain
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D000943:Antigens, Differentiation / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D007107:Immune System / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D055611:Natural Killer T-Cells / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000943:Antigens, Differentiation; D018106:CD28 Antigens; D016207:Cytokines; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic