Increased frequency of myeloid-derived suppressor cells facilitating skin allograft survival in aged mice

Background More and more aged people have organ transplantation recently. Aging process may have an influence on immunity, which conducts an adjustment of immunosuppressive agents to prevent adverse effects. Understanding of aging effects on immunity will be helpful for post-transplant care of aged recipients. Results A mouse model using C3H mice as donors and aged/young C57BL/10J mice as recipients was employed to study the aging effects on immunity. The frequency of CD4 + , CD8 + and native CD4 + foxp3 + regulatory T-cells in the spleen were not different between aged and young mice. However, the frequency of CD11b + Gr-1 + myeloid-derived suppressor cells (MDSC) was higher in aged mice (4.4 ± 1.4% versus 1.6 ± 1.1%, p=0.026). To measure cytokines in the serum, the level of TGF-β was higher in aged mice than in young mice (21.04 ± 3.91ng/ml versus 15.26 ± 5.01ng/ml, p = 0.026). In vitro, enriched T-cells from aged mice had lower proliferation capacity (0.350±0.003 O.D. versus 0.430±0.017 O.D. at responders/stimulatory cells = 100/1) and lower Ag-specific cytotoxic ability (21.2 ± 3.0% versus 39.3 ± 4.8% at target cell/effector cells = 1/100, p=0.003) than T-cells from young mice. In vivo, the skin allografts survived on aged recipients was 19.7 ± 5.2 days, compared 11.9 ± 4.1 days on young mice (p = 0.005). When entinostat was applied to aged mice to block MDSC, the survival of skin allografts was shorten to 13.5 ± 4.7 days which was not different from the survival on young mice (p = 0.359). Conclusion The allogeneic immunity was lower in aged than in young mice evidenced by a higher frequency of MDSC, higher serum level of TGF-β, decreased function of T-cells, and easy-to-induced regulatory T-cells in aged mice. Blocking the function of MDSC reversed the low immunity in aged mice and cause skin allograft rejection similar to young recipients.