Interaction of programmed cell death‐1(PD‐1) with its ligand PD‐ligand 1(PD‐L1) has a co‐inhibitory function in NKT cells

Natural killer T cells (NKT cells) are a distinct subset of T lymphocytes that have invariant T cell receptor (TCR) restricted to CD1d, the MHC class I like‐protein. It is well known that the response of the NKT cells to glycolipids presented by CD1d critically affects innate and adaptive immune response. In the NKT cell response to antigens, co‐stimulatory pathway related to co‐stimulatory molecules such as CD28, ICOS, GITR has been established. However, expression of co‐inhibitory molecules on NKT cells or involvement of co‐inhibitory pathway in the NKT cell response is poorly investigated. We show here that programmed cell death‐1 (PD‐1) and its ligand PD‐L1, known as co‐inhibitory molecules in the interaction of conventional T cells with antigen presenting cells (APCs), were expressed on NKT cells and their interaction could modulate activation of NKT cells as a co‐inhibitors. We found that PD‐1 and PD‐L1 was constitutively expressed on naïve NKT cells and that expression of PD‐L1 was increased at early time points in activation of NKT cell with alpha‐galactosylceramide (aGC). In addition, the blockade of the interaction of PD‐1 and PD‐L1 by blocking monoclonal antibodies led to increase levels of IFN‐γ in sera from aGC‐treated mice. Our findings suggest that the interaction of PD‐1 with PD‐L1 can be defined as a novel co‐inhibitory pathway to regulate activation of NKT cells by antigens.