‘Adjuvant Conditioned’ Myeloid Derived Suppressor Cells Prolong Islets Graft Survival Through IL-10 Production
1Department of Surgery, Boston Children's Hospital, Boston, MA, 2Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
Meeting: 2022 American Transplant Congress
Abstract number: 1245
Keywords: Immunosuppression, Islets
Topic: Basic Science » Basic Science » 08 - Innate Immunity; Chemokines, Cytokines, Complement
Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Type: Poster Abstract
Date: Monday, June 6, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Advances in immunosuppression have been relatively stagnant over the last 2 decades and transplant patients continue to experience morbidity associated with immunosuppression regimens. Through ‘adjuvant conditioning’ (AC), a process by which an adjuvant is administered multiple times in succession, our preliminary data demonstrates that myeloid derived suppressor cells (MDSCs) expand, potently suppress T cell responses in vitro, and prolong the survival of an MHC mismatched islet graft in mice. Many investigators have demonstrated several mechanisms by which MDSCs suppress adaptive immune responses, including upregulation of PD-L1 and IL-10 production. However, the mechanism by which AC MDSCs suppress T cell responses and protect alloislets is unclear.
*Methods: For ‘adjuvant conditioning’, C57BL/6 mice were administered with 200ul of alum intraperitoneally every other day for 3 doses. MDSC surface markers and Intracellular production of IL-10 was assayed via flow cytometry. MDSCs isolated from either alum treated animal spleens or naïve splenocytes were culture with CFSE labelled naïve CD4+ T cells in vitro to assess their suppressive function. BALB/c islets were transplanted under the renal capsule of STZ conditioned C57BL/6 mice. In vivo and in vitro blocking of IL-10 was achieved using anti-IL-10 antibody.
*Results: Following adjuvant conditioning (AC), AC MDSCs upregulated PDL1 expression. In addition, both AC monocyte-MDSCs (25.88%±15.04% vs 5.52%±1.61%, P=0.0491) and granulocyte-MDSCs (34.7%±10.08% vs 10.54%±4.92%, P=0.0061) produced higher amounts of intracellular IL-10 than saline treated cells. In addition, in vitro blockade of IL-10, but not PD-L1, reversed the T cell suppression mediated by AC MDSCs. Finally, blockade of IL-10 in vivo reversed the observed protective effect of adjuvant administration on the rejection of alloislets.
*Conclusions: Our data suggest an important role for MDSC mediated IL-10 production in the suppression of alloimmunity following recipient adjuvant conditioning. Adjuvant conditioning could be a useful strategy to reduce the overall immunosuppression medication burden to transplant patients.
To cite this abstract in AMA style:Ge J, Ott L, Das A, Markmann J, Cuenca A. ‘Adjuvant Conditioned’ Myeloid Derived Suppressor Cells Prolong Islets Graft Survival Through IL-10 Production [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/adjuvant-conditioned-myeloid-derived-suppressor-cells-prolong-islets-graft-survival-through-il-10-production/. Accessed March 25, 2023.
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