Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses
Saikiran K. Sedimbi, Thomas Hägglöf, Manasa G. Garimella, Shan Wang, Amanda Duhlin, Ana Coelho, Katrine Ingelshed, Emma Mondoc, Stephen Malin, Rikard Holmdahl, David P. Lane, Elizabeth A. Leadbetter, Mikael C. I. Karlsson
Abstract
Significance i NKT cells can both provide help and inhibit B cell responses. Our data show that when i NKT cells are activated with the glycolipid agonist αGalCer together with the inflammatory cytokine IL-18, they switch from regulating autoreactive B cells to promoting their expansion. As a consequence, autoreactive B cell responses remain unchecked by i NKT cells. The glycolipid αGalCer has been shown to have promising effects when administered as an adjuvant to achieve a better response to vaccines, as an antitumor agent, as well as in the regulation of autoimmunity. Our results highlight a facet of αGalCer-mediated i NKT cell activation in the context of inflammation and have broad implications for understanding the regulation of autoimmunity and use of αGalCer in therapy.