Invariant Natural Killer T lymphocytes (iNKT) are hybrids between innate and adoptive immunity exerting their effector functions binding glycolipids. Endogenous ligands can also stimulate iNKT to perform their functions¹. However, they may also play a protective role as demonstrated by studies underling their capability to elicit a regulatory potential. This novel potential was recently investigated by our group in human peripheral iNKT.To this aim, we generated iNKT cell lines from the peripheral blood of healthy donors (10 subjects) upon stimulation with a-GalCer, IL-2 and IL-15 for 2 weeks. iNKT cells were then sorted to more than 98% pure population and iNKT cell lines were then treated with different stimuli commonly used to generate in vitro regulatory T cells, namely TGF-β and rapamicyn for 3 to 5 days.  At the end of the culture, iNKT cells were extensively washed and used to suppress proliferation of alloreactive CFSE-labelled T cells².Upon culture with either rapamicyn or TGF-b, iNKT cells acquired the capability to inhibit proliferation of T cells after stimulation with anti-CD3/CD28. The inhibitory activity of rapamicyn- or TGF-b-treated iNKT cell lines was dependent by the numbers of regulatory cells.We performed a detailed phenotypic characterization of these inhibitory cells which are typically expressed by CD4+ Tregs. iNKT cells didn't express any of these markers even after pretreatment with rapamycin or TGF-b.To give insight into the mechanism by which  iNKT suppress T cell proliferation, we performed transwell experiments finding that inhibition of T cell proliferation seem to be contact- and soluble factor-dependent. Data obtained show that regulatory iNKT cells were capable to inhibit proliferation of T cells even when phisically separated by effector cells. Further studies thus are required to determine the relative contributions of  cytokines and/or other soluble factors and/or surface molecules involved in  regulation of T cell proliferation  by regulatory iNKT cells.