Abstract
Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of V2neg 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 V2neg T cells may also be expanded with age. Our results show that V2neg 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 center dot 0001). Furthermore, while V2neg 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, V2neg 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, V2neg T cells demonstrate effector T cell functions, suggesting additional requirements for activation. In summary, V2neg 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 V2neg T cells towards tumour cells, the composition of T cell subsets may also have implications for risk of developing cancer in elderly people.