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Increased Frequency of Myeloid-Derived Suppressor Cells Contributing to Prolong Skin Allograft Survival in Aged Mice

W. Lee, Y. Wang, T. Wu, C. Cheng, C. Lee, T. Wu, H. Chou, K. Chan

General Surgery, Chang-gung Hospital, Taoyuan, Taiwan

Meeting: 2019 American Transplant Congress

Abstract number: D52

Keywords: Age factors, Graft survival, Mice, Transforming growth factor-beta (TGF-b)

Session Information

Session Name: Poster Session D: Tolerance / Immune Deviation

Session Type: Poster Session

Date: Tuesday, June 4, 2019

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Currently, aged people are increasing and more and more aged people have organ transplantation. The immunity in aged people is weaker than young people. Regular immunesuppression regimen may become over-immunosuppression for aged people and cause morbidity. However, the difference of immunity between aged and young hosts were not really clear. This study aims to explore the immunological difference between aged and young hosts in animal model.

*Methods: 8-12 week-old C3H mice were used as donors. 8-12 week-old C57BL/10J (B10) mice were employed young recipients and 12-month-old B10 mice were employed as aged recipients. The population of immune cells in the spleen were analyzed by flow cytometry after the cells were stained by a panel of monoclonal antibodies. Allogeneic skin transplantation was performed by attaching a 1×1 cm C3H skin flap to the flank of B10 young or aged mice.

*Results: The results showed that the frequency of CD4+, CD8+ and native CD4+foxp3+ regulatory T-cells in the spleen were not different between old and young mice. However, the frequency of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) (4.4±1.4% versus 1.6±1.1%, p=0.026) and serum TGF-β (21.04 ± 3.91ng/ml versus 15.26 ± 5.01ng/ml, p = 0.026) was higher in aged mice than in young mice. In vitro, the T-cells from aged mice had lower proliferation capacity (0.350±0.003 O.D. versus 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 21.6±4.4 days, compared 12.5±4.3 days on young mice (p <0.001). While the aged mice were fed with entinostat to block the effect of MDSC, the skin allografts survive was shortened to 8.7±1.2 days.

*Conclusions: The aged mice have higher frequency of MDSC, higher serum level of TGF-β and lower function of T-cells than young mice. The higher frequency of MDSC and serum level of TGF-β in aged mice implied low immunity in aged mice. Blocking the effect of MDSC reversed the aging effect on allogeneic skin transplantation.

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To cite this abstract in AMA style:

Lee W, Wang Y, Wu T, Cheng C, Lee C, Wu T, Chou H, Chan K. Increased Frequency of Myeloid-Derived Suppressor Cells Contributing to Prolong Skin Allograft Survival in Aged Mice [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/increased-frequency-of-myeloid-derived-suppressor-cells-contributing-to-prolong-skin-allograft-survival-in-aged-mice/. Accessed May 9, 2025.

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