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Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4 T-cells
Authors:Piotr Trzonkowski  Alicja D?bska-?lizień  Magdalena Jankowska  Manuela Carvalho-Gaspar  Gra?yna Moszkowska  Natalie Mills  Jolanta My?liwska
Affiliation:a Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Ul. D?binki 1, 80-211 Gdańsk, Poland
b Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdańsk, Poland
c Department of Immunology, Medical University of Gdańsk, Poland
d Transplantation Research Immunology Group, Nuffield Department of Surgery, University of Oxford, UK
Abstract: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.
Keywords:Aza, azathioprine   ChAD, chronic allograft dysfunction   CsA, cyclosporine   MMF, mycophenolate mofetil   pred, prednisone   PBMC, peripheral blood mononuclear cells   tacro, tacrolimus   Tcm, central memory T-cells   Tem, effector memory T-cells   TemRA, effector memory CD45RA T-cells   Tm, memory T-cells   Tn, naï  ve T-cells   rapa, rapamycin
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