Strong Engagement of CD137 Suppresses Graft-Versus-Host Disease Through Dendritic Cells
1Ulsan University Hospital, Ulsan, Korea, Republic of, 2Nephrology, Ulsan University Hospital, Ulsan, Korea, Republic of, 3Biomedical Research Center, Ulsan University Hospital, Ulsan, Korea, Republic of, 4Surgery, Ulsan University Hospital, Ulsan, Korea, Republic of
Meeting: 2020 American Transplant Congress
Abstract number: D-343
Keywords: Antigen presentation, Co-stimulation, Graft-versus-host-disease
Session Information
Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: We previously demonstrated that anti-CD137 agonist prevent acute graft-versus-host disease (GVHD) and chronic GVHD in the parent-into-unirradiated F1 acute or chronic GVHD model. Although activation-induced dell death of donor T cells is one mechanism of anti-CD137-mediated suppression of GVHD, its detailed process remains to be clarified.So we investigated the role of DC with anti-CD137 in GVHD suppression.
*Methods: Induction of cGVHD Single-cell suspensions in PBS were prepared from the spleens and lymph nodes of female bm12 mice. Chronic GVHD was induced by transfer of 8 x 107 of bm12 cells into the tail vein of female wild-type and CD137-/- mice. Immediately thereafter, 200 μg of anti-CD137 mAb (3E1) or control Ig was intraperitoneally administered.MACS purification and FACS sorting of DC subsets Splenocytes were prepared by digestion. For purification of CD11b+ DCs, CD8α– DCs were first removed by a negative selection using anti-CD8α-microbeads . The remained cells were positively selected using anti-CD11c-microbeads . For purification of CD8α+ DCs, a negative selection of splenocytes with anti-CD11b-microbeads and a positive selection with anti-CD11c-microbeads were sequentially performed. For FACS sorting of DC subsets, DCs were first enriched from splenocytes using anti-CD11c-microbeads. The enriched cells were then stained with anti-CD11 and anti-CD8α+ mAb at 4 °C for 30 min. After the cells were washed twice with PBS buffer containing 1% BSA, CD8α+ and CD11b+ DCs were sorted using FACSAria III.
*Results: . Here, we report that in vivo engagement of CD137 in chronic GVHD mice massively induced the generation of PD-L1hiPD-L2+OX40+IL-10+CD11b+ dendritic cells (DCs) and such regulatory DCs could prevent either chronic or acute GVHD. IL-10 is required for these regulatory DCs to expand conventional Treg cells. Interestingly, a lower number of Treg cells suppressed acute GVHD compared to chronic GVHD, suggesting that autoantibody production is governed by less stringent immunoregulation. In some GVHD models, however, anti-CD137-primed DCs potently induced activation-induced cell death of donor T cells.
*Conclusions: . In conclusion, our study indicates that anti-CD137 antibody suppresses acute and chronic GVHD by different mechanisms involving distinct DCs subsets.
To cite this abstract in AMA style:
Cho H, Lee J, Kwon B, Park S, Park H, Yoo K, Park K, Kim J, Kang S. Strong Engagement of CD137 Suppresses Graft-Versus-Host Disease Through Dendritic Cells [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/strong-engagement-of-cd137-suppresses-graft-versus-host-disease-through-dendritic-cells/. Accessed December 12, 2024.« Back to 2020 American Transplant Congress