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Publication : Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1.

First Author  Wang J Year  2009
Journal  J Immunol Volume  182
Issue  11 Pages  6644-7
PubMed ID  19454657 Mgi Jnum  J:148876
Mgi Id  MGI:3847043 Doi  10.4049/jimmunol.0804050
Citation  Wang J, et al. (2009) Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1. J Immunol 182(11):6644-7
abstractText  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.
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