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Expansion of Myeloid Derived Suppressor Cells Following Alum Administration

A. G. Cuenca, N. J. Feeney, K. Deng, C. G. Rickert, J. F. Markmann

Massachusetts General Hospital, Boston, MA

Meeting: 2019 American Transplant Congress

Abstract number: C42

Keywords: Immunosuppression, Inflammation

Session Information

Date: Monday, June 3, 2019

Session Name: Poster Session C: Innate Immunity; Chemokines, Cytokines, Complement

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

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

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*Purpose: Immunosuppressive medications, such as calcineurin inhibitors, are critical to the survival of the transplant allograft but come with significant morbidity to the recipient and strategies to reduce current immunosuppressive regimens are needed. Myeloid derived suppressor cells (MDSCs), comprised of both neutrophil (LyG+CD11b+) and monocyte (Ly6CloCD11b+) populations, have been demonstrated to have potent immunosuppressive properties in numerous studies through a variety of mechanisms including the expansion of regulatory T cells. Therefore strategies to augment these suppressor cell myeloid populations in vivo could be used to promote allograft survival while reducing the amount of immunosuppression medication burden to the patient

*Methods: To study this, C57Bl/6 mice were administered the classic adjuvant, Alum, intraperitoneally every other day for a week (total of 3 treatments). Spleens and blood were taken and analyzed by flow cytometry for both LyG+CD11b+ populations and Ly6CloCD11b+ populations at different time points post final Alum injection.

*Results: We found that Alum treated mice had a statistically significant expansion in the percentage of the granulocyte MDSCs (LyG+CD11b+) at 24, 48 hours and 7 days (9.4, 6.8, and 7.9 %, respectively) versus the untreated animals (1.2%). We observed a similar statistically significant expansion in the monocyte MDSCs (Ly6CloCD11b+) at 24, 48, and 7 days (10.6, 8.3, and 12.6 %, respectively) versus the untreated animals (2.0%). Analysis of the blood at these time points yielded similar results.

*Conclusions: These data suggest that by using Alum, we can induce the expansion of both granulocyte and monocyte myeloid derived cell populations. Future studies will aim to optimize the timing of allograft transplantation following Alum induced MDSC expansion to promote graft survival. Importantly, by using this therapeutic strategy, we can promote intrinsic host immunosuppression and allograft tolerance, as well as decrease the overall intensity and duration of immunosuppressive regimens.

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To cite this abstract in AMA style:

Cuenca AG, Feeney NJ, Deng K, Rickert CG, Markmann JF. Expansion of Myeloid Derived Suppressor Cells Following Alum Administration [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/expansion-of-myeloid-derived-suppressor-cells-following-alum-administration/. Accessed April 15, 2021.

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