IL-10-Secreting CD8<sup>+</sup> T Cells Specific for Human Cytomegalovirus (HCMV): Generation, Maintenance and Phenotype
Sarah E. Jackson,
George X. Sedikides,
Veronika Romashova,
Georgina Okecha,
Ester B. M. Remmerswaal,
Frederike J. Bemelman,
John H. Sinclair,
Mark R. Wills
Affiliations
Sarah E. Jackson
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
George X. Sedikides
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
Veronika Romashova
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
Georgina Okecha
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
Ester B. M. Remmerswaal
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, 1019 Amsterdam, The Netherlands
Frederike J. Bemelman
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, 1019 Amsterdam, The Netherlands
John H. Sinclair
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
Mark R. Wills
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge Biomedical Campus, School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
HCMV-specific CD8+ T-cells are potent anti-viral effector cells in HCMV infected individuals, but evidence from other viral infections suggests that CD8+ T-cells can also produce the immunomodulatory cytokine IL-10. In this work we show that there are HCMV-specific IL-10 CD8+ T-cell responses in a cohort of individuals aged 23–76 years of age, predominantly directed against the HCMV proteins known to be expressed during latent infections as well as towards the proteins US3 and pp71. The analysis of HCMV-specific responses established during primary infection has shown that the IL-10 responses to US3 and pp71 HCMV proteins are detectable in the first weeks post infection, but not the responses to latency-associated proteins, and this IL-10 response is produced by both CD8+ and CD4+ T-cells. Phenotyping studies of HCMV-specific IL-10+ CD8+ T-cells show that these are CD45RA+ effector memory cells and co-express CD28 and CD57, however, the expression of the inhibitory receptor PD-1 varied from 90% to 30% between donors. In this study we have described for the first time the HCMV-specific IL-10 CD8+ T-cell responses and have demonstrated their broad specificity and the potential immune modulatory role of the immune response to HCMV latent carriage and periodic reactivation.
