Increased numbers and functional activity of CD56+ T cells in healthy cytomegalovirus positive subjects

Authors

  • Mazen Almehmadi,

    1. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection & Global Health, University of Liverpool, Liverpool, UK
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  • Brian F. Flanagan,

    1. Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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  • Naeem Khan,

    1. Department of Clinical Immunology Service, University of Birmingham, Birmingham, UK
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  • Suliman Alomar,

    1. Zoology Department, King Saud University, Riyadh, Saudi Arabia
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  • Stephen E. Christmas

    Corresponding author
    1. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection & Global Health, University of Liverpool, Liverpool, UK
    • Correspondence: Dr Stephen E. Christmas, Department of Clinical Infection, Microbiology & Immunology, Institute of Infection & Global Health, University of Liverpool, 8 West Derby Street, Liverpool L69 7BE, UK. Email: sechris@liv.ac.uk

      Senior author: Stephen E. Christmas

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Summary

Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. Proportions of CD56+ T cells were found to be highly significantly increased in cytomegalovirus-seropositive (CMV+) compared with seronegative (CMV) healthy subjects (9·1 ± 1·5% versus 3·7 ± 1·0%; P < 0·0001). Proportions of CD56+ T cells expressing CD28, CD62L, CD127, CD161 and CCR7 were significantly lower in CMV+ than CMV subjects but those expressing CD4, CD8, CD45RO, CD57, CD58, CD94 and NKG2C were significantly increased (P < 0·05), some having the phenotype of T effector memory cells. Levels of pro-inflammatory cytokines and CD107a were significantly higher in CD56+ T cells from CMV+ than CMV subjects following stimulation with CMV antigens. This also resulted in higher levels of proliferation in CD56+ T cells from CMV+ than CMV subjects. Using Class I HLA pentamers, it was found that CD56+ T cells from CMV+ subjects contained similar proportions of antigen-specific CD8+ T cells to CD56 T cells in donors of several different HLA types. These differences may reflect the expansion and enhanced functional activity of CMV-specific CD56+ memory T cells. In view of the link between CD56 expression and T-cell cytotoxic function, this strongly implicates CD56+ T cells as being an important component of the cytotoxic T-cell response to CMV in healthy carriers.

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