Ageing of long-term allogeneic hematopoietic cells recipients compared to their donors

Abstract

Background: Ageing is a complex phenomenon that leads to decreased proliferative activity, loss of function of the cells, and cellular senescence. Senescence of the immune system exacerbates individual’s immune response, both humoral and cellular but increases the frequency of infections. We hypothesized that physiological ageing of adaptive immune system occurs in recipients of allogeneic hematopoietic cells transplant (allo-HCT) at faster rate when compared to their respective donors since the small number of donor cells undergo immense proliferative stress restoring recipients hematopoiesis. We compared molecular characterizations of ageing between recipients and donors of allo-HCT: telomeric length, proinflammatory cytokines concentration, and immunophenotypic changes in main lymphocyte subsets – CD4+, CD8+, CD19+, CD56+.Results: Median telomeric length (TL) of CD8+ lymphocytes was significantly longer in donors compared to recipients (on average 2,1kb and 1,7kb respectively, p = 0,02). Similar trends were observed for CD4+ and CD19+ although the results did not reach statistical significance. We have also found trends in the immunophenotype between recipients and donors in the subpopulations of CD4+ (naïve and effector memory), CD8+ Eomes+ and B-lymphocytes (B1 and B2). When grouped according to the history of infections, there were differences between recipients in the TNF-a and Il-4 concentrations. They were higher in the recipients with lower infection number p=0,05 and p=0,003 respectively. Lower infection risk recipients had also significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p=0,04.Conclusions: Our results support the hypothesis of accelerated ageing of the recipients lymphocytes observed mainly in CD8 subset compared to their respective donors. Quantitative changes in recipients immunophenotype in some lymphocyte subsets resemble physiological ageing-associated changes. No difference in cytokine concentrations suggests that inflammageing does not increase in allo-HCT recipients, however a lower infection numbers in HCT recipients seems to be associated with increased concentration of proinflammatory cytokines and increased percentage of NK cells. The GVHD does not affect the rate of ageing. Therefore, the differences between recipients and donors cells may result from the proliferative stress in the early period after allo-HCT and the difference between hosts and recipients microenvironments, the only other variable that may influence the identical cells originating from donor hematopoiesis.