Immunological discrepancy in aged mice facilitates skin allograft survival

Aging (Albany NY). 2021 Jun 22;13(12):16219-16228. doi: 10.18632/aging.203152. Epub 2021 Jun 22.

Abstract

More and more aged people are undergoing organ transplantation. Understanding aging effects on immunity will be helpful for post-transplantation care and adjustment of immunosuppressants for aged recipients. A mouse model, using C3H mice as donors and aged/young C57BL/10J mice as recipients, was employed to study aging effects on immunity. The results showed that frequency of myeloid-derived suppressor cells (MDSC) and level of TGF-β was higher in aged mice than in young mice (4.4 ± 1.4% versus 1.6 ± 1.1%, p = 0.026 for MDSC; 21.04 ± 3.91 ng/ml versus 15.26 ± 5.01 ng/ml, p = 0.026 for TGF-β). In vivo, skin allograft survived longer on the aged than on young mice (19.7 ± 5.2 days versus 11.9 ± 4.1 days, p = 0.005). When entinostat was applied to block MDSC, the survival of skin allografts on aged mice was shorten to 13.5 ± 4.7 days which was not different from the survival on young mice (p = 0.359). In conclusion, allogeneic immunity was different in aged from young mice in high frequency of MDSC and high serum level of TGF-β. Blocking the function of MDSC reversed the low immunity in aged mice and caused skin allograft rejection similar to young recipients.

Keywords: aged recipient; immunosuppression; myeloid-derived suppressor cell; organ transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / blood
  • Aging / immunology*
  • Animals
  • Antigen Presentation / immunology
  • Cytokines / blood
  • Cytotoxicity, Immunologic
  • Graft Survival / immunology*
  • Kaplan-Meier Estimate
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Skin Transplantation*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Cytokines