Age‐ and sex‐mediated differences in T lymphocyte populations of kidney transplant recipients

Abstract

Background: Graft failure rates increase through childhood and adolescence, decline in adulthood, and are higher in female than male kidney transplant recipients (KTR) until middle age. We aimed to describe age-and sex-related differences in T-cell subsets among KTR to determine which differences may help to explain the differences in kidney graft failure rates. Methods: Effector T (Teff)-cell and regulatory T (Treg)-cell phenotypes in PBMCsfrom healthy controls and KTR, who were at least 1 year post-transplant with stable graft function under immunosuppression, were analyzed by flow cytometry. The effects of age, sex, and status (KTR or control) were analyzed using linear regressions. Results:We enrolled 20 male and 21 female KTR and 20 male and 20 female controls between 3 and 29 years of age. CD3+ T-cell frequencies were not associated with age or sex but were higher in KTR than controls. There were no differences in CD4+ and CD8+ frequencies. Th1 (IFNγ+ IL-4− IL-17A−) and Th17 (IL-17A+) frequencies within the CD4+ T-cell population were higher at older ages. The frequencies of FOXP3 + Helios + Treg cells in CD4+ CD25+ CD127− T cells were lower in females than males and in KTR than controls.Conclusions: Increasing frequencies of Th1 and Th17 cells with increasing age mirrors the increasing graft failure rates from childhood to young adulthood. Importantly, sex differences in frequencies of circulating Treg cells may suggest a role in the sex differences in graft failure rates.

Age-dependent Sex Differences in Graft Loss After Kidney Transplantation

“…For example, the possibility that young females have a more potent immune response than young males should be considered. 40 The impact of cyclical sex hormones on the pharmacokinetics of immunosuppressive medications should also be investigated. Finally, the explanation for superior graft survival among older women than men should be sought.…”

The immunomodulation role of Th17 and Treg in renal transplantation

“…In addition, Th17 levels in patients with CKD who have not undergone KT are also lower than those after KT, suggesting that immune response is the cause of the development of CKD after transplantation ( 45 , 51 ). Retrospective studies have found that the increase in the proportion of Th17 cells is consistent with the increase in the rate of graft failure ( 52 ). In addition, Th17 infiltration of allograft has a certain indicator effect on transplantation prognosis and anti-rejection response ( 53 ).…”

Sex difference and immunosenescence affect transplantation outcomes

“…A study of kidney transplantation among 3–29-years-old showed that Th1 (IFNγ + IL-4 − L-17A − ) and Th17 (IL-17A + ) frequencies within CD4 + T cells could be higher at older ages, but the frequencies of FOXP3 + Treg cells in CD4 + CD25 + CD127 − T cells were lower in females than in males ( 38 ). This report did not show serum estrogen levels; however, women in their twenties could be estimated to have higher estrogen levels than pre-adolescent and post-menopausal women.…”