TY - JOUR
T1 - IL-10-Secreting CD8+ T Cells Specific for Human Cytomegalovirus (HCMV)
T2 - Generation, Maintenance and Phenotype
AU - Jackson, Sarah E.
AU - Sedikides, George X.
AU - Romashova, Veronika
AU - Okecha, Georgina
AU - Remmerswaal, Ester B. M.
AU - Bemelman, Frederike J.
AU - Sinclair, John H.
AU - Wills, Mark R.
N1 - Funding Information: This research was funded by the Medical Research Council (MRC:UKRI) grants MR/K021087, MR/S00081X/1 and MR/S00981X/1. Funding Information: We gratefully acknowledge the participation of all Cambridge NIHR BioResource volunteers, and we thank the Cambridge BioResource staff for their help with volunteer recruitment. The Cambridge BioResource is funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) and the NHS Blood and Transplant (NHSBT) service. This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub. Publisher Copyright: © 2022 by the authors.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - IL-10 secretion
KW - T regulatory cells
KW - human cytomegalovirus (HCMV)
KW - immunomodulation
UR - http://www.scopus.com/inward/record.url?scp=85144666453&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/pathogens11121530
DO - https://doi.org/10.3390/pathogens11121530
M3 - Article
C2 - 36558866
SN - 2076-0817
VL - 11
JO - Pathogens
JF - Pathogens
IS - 12
M1 - 1530
ER -