CD6 is a highly specific marker of T cells and a risk factor for multiple sclerosis; however, its cellular function in the latter context is unclear. In the Proceedings of the National Academy of Sciences, Lin and colleagues develop a CD6-knockout mouse (KO) and a mouse with knock-in human CD6 on a CD6-knockout background (KI) to investigate CD6's role in experimental autoimmune encephalitis. The KO mice are almost totally resistant to this disease and show less induction of the TH1 and TH17 subsets of helper T cells in vitro. Although KO T cells have higher expression of activation markers, which suggests that CD6 is a negative regulator, they show less proliferation, a greater propensity to die by apoptosis and impaired transmigration across endothelial layers. Finally, antibodies generated against human CD6 protect KI mice in a non-depleting manner. CD6 is probably a negative regulator of the activation of T cells and also seems to be required for their survival and entry into the central nervous system and could be an important target in multiple sclerosis.

Proc. Natl. Acad. Sci. USA (16 February 2017) doi:10.1073/pnas.1615253114