Ageing-resembling phenotype 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 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 2,1 kb and 1,7 kb 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). Lower infection risk recipients had also a significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p = 0,04. Conclusion Our data do not support the initial hypothesis of accelerated aging in the long term all-HCT recipients with the exception of the recipients lymphocytes (mainly CD8+) which present some molecular features, characteristic for physiological ageing (telomeric shortening, immunophenotype) when compared to their respective donors. However, a history of lower infection numbers in HCT recipients seems to be associated with increased percentage of NK cells. The history of GVHD seems not to affect the rate of ageing. Therefore, it is safe to conclude that the observed subtle differences between recipients’ and donors’ cells result mainly from the proliferative stress in the early period after allo-HCT and the difference between hosts’ and recipients’ microenvironments.

Long-term allogeneic hematopoietic cells transplantation survivors proinflammatory cytokine profile compared to their respective donors and immunophenotype differences depending on GvHD history and infection status

“…The statistical analysis was performed by STATISTICA 12.0 and with Microsoft Exel, detailed analysis was described according to Czarnogórski et al [6]. The W Shapiro-Wilk test, and the Leven's (Brown-Forsythe) test were used.…”

“…We were particularly interested in the features of postulated 'inflammaging'. We also compared the same cytokine profile of the recipients when grouped according to infectious status (low vs intermediate/high) (see Czarnogórski et al [6]). We hypothesized that allo-HCT recipients should have higher concentrations of proinflammatory cytokines as a robust indicator of aging.…”

“…We reported recently our observations regarding the changes in immunophenotype and shortened telomeres in CD8+ lymphocyte subpopulation in long-term allo-HCT recipients compared to their respective donors [6]. Here, we present data on the proinflammatory cytokine profile of the same population of patients, i.e.…”

“…Patients were stratified according to their history of chronic GvHD status (yes vs. no) and infectious complications according to an infection risk status score developed for the purpose of this study [6].…”

“…The prevalence of chronic graft versus host disease among recipients was 40%. Infection risk status was assessed according to Czarnogórski et al [6]: 12 low risk recipients and 8 high risk recipients.…”