Anti-CD1d Monoclonal antibody, clone 62.2 [PerCP-eFluor® 710]

Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells. Finally, we discuss future perspectives to better harness the potential of NKT cells for cancer therapy.

Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+) CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+) CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(h)i Bregs by flow cytometry. FasL expression in CD5(+)CD1d(hi) cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5(+)CD1d(hi) B cells although the IL-10 production was up-regulated in this subset. In addition, LPS and other B10-cell inducers increased the expression of surface molecules like CD86 and CD25, which are correlated to the regulatory functions of B cells. Furthermore, NF-kappa 3 and NF-AT inhibitors decreased the TLR4-activated FasL expression in CD5(+) CD1d(hi) B cells. Then we sorted splenic CD5(+) CD1d(hi) Bregs using flow cytometry and found that TLR4-activated CD5(+) CD1d(hi) Bregs suppressed the proliferation of CFSE-labeled CD4(+) T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5(+) CD1d(hi) B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5(+)CD1d(hi) B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5(+) CD1d(hi) Bregs might participate in the regulation of inflammatory diseases.