title: Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age.
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.
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Alejenef
authors.forename: A
authors.initials: A
authors.lastname: Pachnio
authors.forename: M
authors.initials: M
authors.lastname: Halawi
authors.forename: S E
authors.initials: SE
authors.lastname: Christmas
authors.forename: P A H
authors.initials: PA
authors.lastname: Moss
authors.forename: N
authors.initials: N
authors.lastname: Khan
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008875:Middle Aged; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: cytomegalovirus; old age; γδ T-cells