title: Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells.
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 > or = 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 TGFbeta 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.
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Ul. Debinki 1, 80-211 Gdańsk, Poland. ptrzon@amg.gda.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: Alicja
authors.initials: A
authors.lastname: Debska-Slizień
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jankowska
authors.forename: Anna
authors.initials: A
authors.lastname: Wardowska
authors.forename: Manuela
authors.initials: M
authors.lastname: Carvalho-Gaspar
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Hak
authors.forename: Grazyna
authors.initials: G
authors.lastname: Moszkowska
authors.forename: Beata
authors.initials: B
authors.lastname: Bzoma
authors.forename: Natalie
authors.initials: N
authors.lastname: Mills
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wood
authors.forename: Jolanta
authors.initials: J
authors.lastname: Myśliwska
authors.forename: Bolesław
authors.initials: B
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D018106:CD28 Antigens