Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells

Compromised immunity is the hallmark of ageing. Paradoxically, it may be “an ally” in facilitating acceptance of allogeneic grafts in the elderly. In this retrospective study we looked for biomarkers of immunosenescence that distinguish elderly recipients less prone to reject kidney allografts.Recruited kidney recipients aged ≥60 or <60 were designated ‘elderly’ and ‘young’, respectively. Both age-groups were divided according to the history of acute rejection. The phenotype, length of telomeres, expression of FoxP3 and proliferative responses were assessed in CD4+ and CD8+ T-cell subsets. In addition, IL6, IL10 and TGFβ were measured on the level of mRNA and serum protein.Acute-rejection-free history in elderly transplant recipients was associated with short telomeres, a decreased proportion of CD28+ T-cells associated with CMV-seropositivity and low proliferation of CD4+ T-cells. In contrast, elderly recipients who experienced acute rejection kept preserved telomere length, had a higher number of functional CD4+CD28+ cells and exhibited vigorous proliferation in vitro. These differences were not found in the young group.The major conclusion of this study is that the impaired condition of CD4+ T-cells, so-called immunosenescence, renders transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients of >60 years of age.