Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age

A. Alejenef, A. Pachnio, M. Halawi, S. E. Christmas, P. A. H. Moss, N. Khan

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17 Citations (Scopus)
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Abstract

Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of Vδ2(neg) γδ T cells in healthy and immunocompromised CMV carriers. Having shown previously that virus-specific CD8(+) and CD4(+) T cell responses are increased significantly in elderly CMV carriers, probably driven by chronic stimulation, we hypothesized that Vδ2(neg) γδ T cells may also be expanded with age. Our results show that Vδ2(neg) γδ T cells are increased significantly in CMV-seropositive healthy individuals compared to CMV-seronegative controls in all age groups. The differences were most significant in older age groups (P < 0·0001). Furthermore, while Vδ2(neg) γδ T- cells comprise both naive and memory cells in CMV-seronegative donors, highly differentiated effector memory cells are the dominant phenotype in CMV carriers, with naive cells reduced significantly in numbers in CMV-seropositive elderly. Although phenotypically resembling conventional CMV-specific T cells, Vδ2(neg) γδ T cells do not correlate with changes in magnitude of CMV-specific CD4(+) or CD8(+) T cell frequencies within those individuals, and do not possess ex-vivo immediate effector function as shown by CMV-specific CD4(+) and CD8(+) T cells. However, after short-term culture, Vδ2(neg) γδ T cells demonstrate effector T cell functions, suggesting additional requirements for activation. In summary, Vδ2(neg) γδ T cells are expanded in many older CMV carriers, demonstrating a further level of lymphocyte subset skewing by CMV in healthy individuals. As others have reported shared reactivity of Vδ2(neg) γδ T cells towards tumour cells, the composition of γδ T cell subsets may also have implications for risk of developing cancer in elderly people.
Original languageEnglish
Pages (from-to)418-428
JournalClinical & Experimental Immunology
Volume176
Issue number3
DOIs
Publication statusPublished - 1 Jun 2014

Keywords

  • γδ T-cells
  • cytomegalovirus
  • old age

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