Abstract
Abstract CD8 T cell exhaustion is an immunosuppressive mechanism by which chronic viruses escape adaptive immune response. Yet, the direct implication of cytokines as well as the precise candidates involved in this process have remained elusive. Here we demonstrate the direct contribution of IL-2 and IL-15 on several aspects of CD8 T cell exhaustion. Using a mouse model of chronic viral infection (LCMV clone-13), we show that IL2Rβ (CD122; the receptor chain common to IL-2 and IL-15) is maintained on CD8 T cells during chronicity. Its expression correlates with deeper exhaustion and selectively marks terminally exhausted CD8 T cells in mice and humans. Adoptive transfer of IL2Rβ−/− P14 CD8 T cells (unresponsive to combined IL-2 and IL-15-dependent signals) revealed that IL-2 and IL-15 directly control the expression of a specific pattern of inhibitory receptors and are mandatory for the development of PD-1hi effectors. Further, IL-2 and IL-15 instigate the arrested development of central memory cells seen during antigen persistence and preclude responsiveness to IL-7-dependent signals. Together, we ascribe a novel role to IL-2 and IL-15 as instigators of CD8 T cell exhaustion during chronic viral infection.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
