CD4+ memory T cells re-expressing CD45RA can be generated from the CD45RA− CD27+ population by the addition of IL-7 and during this process these cells down-regulated expression of IL-7R and Bcl-2 and so resemble their counterparts in vivo. Finally we showed that the proportion of CD45RA+ CD27− CD4+ T cells of multiple specificities was significantly higher in the bone marrow than the blood of the same
individuals, suggesting that this may be a site where these cells are generated. The function of the immune system declines with age leading to increased susceptibility to infectious diseases and poor responses to vaccination.1 With the demographic shift towards an older age in many countries it is of increasing importance to understand the Navitoclax solubility dmso nature of the dysfunctional immunity in older subjects.2 This information will provide information on possible strategies PD-0332991 price for intervention to boost immunity during ageing. The immune dysfunction in older humans is partly the result of thymic involution, which restricts the production of naive T cells in older individuals, compromising their ability to respond to new antigens.3 In addition, memory T cells, especially those that are specific for antigens that are encountered frequently, are driven to differentiate
continuously towards an end-stage, marked by poor survival, telomere erosion, replicative senescence3 and functional exhaustion.4 This may result in ‘holes’ in the T-cell repertoire as T cells that are specific for certain antigens are lost, which in turn may make older humans susceptible to certain infectious agents.2 However, instead of the potential loss of specific T cells through replicative senescence, immune dysfunction during ageing may also arise from accumulation of certain T-cell populations. Longitudinal studies have defined a cluster Cyclin-dependent kinase 3 of immune parameters in healthy older individuals, which are predictive of significantly decreased 2-year and
4-year survival of subjects over 80 years of age (reviewed in Derhovanessian et al.5). These parameters include a CD4 : CD8 ratio of < 1, which is the result of clonal expansion of highly differentiated CD8+ CD28− T cells, cytomegalovirus (CMV) seropositivity and elevated levels of pro-inflammatory cytokines in the serum.5 Furthermore, a large proportion of the expanded CD8+ T cells in older subjects may be CMV-specific.6–8 Therefore, although CMV infection is harmless to healthy young individuals, infection with this virus may have a previously unappreciated role in immune dysfunction during ageing, which is associated with the accumulation of CMV-specific T cells. This suggests that CMV infection may induce the accumulation of CD8+ effector T cells that hinder the function of other memory T-cell populations.