Model for CD1d-dependent CLL disease progression. Gorini and colleagues postulate that chronic stimulation of NKT cells with high levels of CD1d/self-ligand complexes on CD1d^hi CLL cells leads to NKT cellular exhaustion. The exhausted NKT cells therefore have a diminished ability to engage and suppress differentiation and function of CD1d⁺ NLCs. Removal of NLC suppression allows them to support CLL cells, thus increasing the chance of disease progression. Images adapted from Servier Medical Art under a Creative Commons CC-BY license.