Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response

Perona-Wright, G. , Kohlmeier, J. E., Bassity, E., Freitas, T. C., Mohrs, K., Cookenham, T., Situ, H., Pearce, E. J., Woodland, D. L. and Mohrs, M. (2012) Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response. Proceedings of the National Academy of Sciences of the United States of America, 109(45), pp. 18535-18540. (doi: 10.1073/pnas.1119133109) (PMID:23091017) (PMCID:PMC3494933)

Abstract

CD8+ T cells are central to the eradication of intracellular pathogens, but they can also act to limit inflammation and immunopathology. During primary respiratory viral infection CD8+ effector T cells release the immunosuppressive cytokine IL-10, which is essential for host survival. Here we report that CD8+ T-cell–derived IL-10 is absent in a recall response. We show in mice that the lack of IL-10 is due to a persistent loss of IL-27 responsiveness in CD8+ memory T cells, caused by down-regulation of the common cytokine receptor, glycoprotein 130. CD8+ memory T cells secreted less IL-10 when activated in the presence of IL-27 than did naïve controls, and retroviral expression of glycoprotein 130 restored IL-10 and reduced IFN-γ production upon restimulation. We demonstrate that human CD8+ memory cells are also characterized by impaired IL-27 responsiveness. Our data suggest that CD8+ T-cell activation involves a persistent loss of specific cytokine receptors that determines the functional potential of these cells during rechallenge infection.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Perona-Wright, Dr Georgia
• Authors: Perona-Wright, G., Kohlmeier, J. E., Bassity, E., Freitas, T. C., Mohrs, K., Cookenham, T., Situ, H., Pearce, E. J., Woodland, D. L., and Mohrs, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 22 October 2012