Human NKT cells direct the differentiation of myeloid APCs that regulate T cell responses via expression of programmed cell death ligands.

ABSTRACT: NKT cells are innate lymphocytes that can recognize self or foreign lipids presented by CD1d molecules. NKT cells have been shown to inhibit the development of autoimmunity in murine model systems, however, the pathways by which they foster immune tolerance remain poorly understood. Here we show that autoreactive human NKT cells stimulate monocytes to differentiate into myeloid APCs that have a regulatory phenotype characterized by poor conjugate formation with T cells. The NKT cell instructed myeloid APCs show elevated expression of the inhibitory ligand PD-L2, and blocking PD-L1 and PD-L2 during interactions of the APCs with T cells results in improved cluster formation and significantly increased T cell proliferative responses. The elevated expression of PD-L molecules on NKT-instructed

SUBMITTER: Hegde S 

PROVIDER: S-EPMC3110565 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature