Abstract
BackgroundAgeing is associated with changes in the immune system with substantial alterations in T-lymphocyte subsets. Cytomegalovirus (CMV) is one of the factors that affect functionality of T cells and the differentiation and large expansions of CMV pp65-specific T cells have been associated with impaired responses to other immune challenges. Moreover, the presence of clonal expansions of CMV-specific T cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious diseases in the elderly. In this study, we analyse the effect of ageing on the phenotype and frequency of CMV pp65-specific CD8 T cell subsets according to the expression of CCR7, CD45RA, CD27, CD28, CD244 and CD85j.ResultsPeripheral blood from HLA-A2 healthy young, middle-aged and elderly donors was analysed by multiparametric flow cytometry using the HLA-A*0201/CMV pp65495–504 (NLVPMVATV) pentamer and mAbs specific for the molecules analysed. The frequency of CMV pp65-specific CD8 T cells was increased in the elderly compared with young and middle-aged donors. The proportion of naïve cells was reduced in the elderly, whereas an age-associated increase of the CCR7null effector-memory subset, in particular those with a CD45RAdim phenotype, was observed, both in the pentamer-positive and pentamer-negative CD8 T cells. The results also showed that most CMV pp65-specific CD8 T cells in elderly individuals were CD27/CD28 negative and expressed CD85j and CD244.ConclusionThe finding that the phenotype of CMV pp65-specific CD8 T cells in elderly individuals is similar to the predominant phenotype of CD8 T cells as a whole, suggests that CMV persistent infections contributes to the age-related changes observed in the CD8 T cell compartment, and that chronic stimulation by other persistent antigens also play a role in T cell immunosenescence. Differences in subset distribution in elderly individuals showing a decrease in naive and an increase in effector-memory CD8 T cells may be relevant in the age-associated defective immune response.
Highlights
Ageing is associated with changes in the immune system with substantial alterations in Tlymphocyte subsets
The results demonstrated that the proportion of naïve A2/CMV-pp65 pentamer-positive CD8 T cells were
CFiDgu8rTe c1ell-subset distribution according to the expression of CCR7 and CD45RA CD8 T cell-subset distribution according to the expression of CCR7 and CD45RA
Summary
Ageing is associated with changes in the immune system with substantial alterations in Tlymphocyte subsets. The presence of clonal expansions of CMV-specific T cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious diseases in the elderly. The CMV phosphoprotein pp (UL83) is the major antigen recognised by T lymphocytes targeting functionally efficient T cell effector responses with massive production of Th1 cytokines and exhibition of CD107a degranulation marker [11]. The percentage of these cells are strikingly expanded and the great majority are CD28-[12,13]. In addition the CD8 T cell subset shows a significant increase of the CD45RA+ CD27- subset, likely as a consequence of acute CMV infection [14]
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