Ex-Vivo Generation of Alloantigen-Specific Immunomodulatory Cells: Elucidating the Mechanistical Synergy of Cell Components
1Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
2Transplantation, Hokkaido University Hospital, Sapporo, Japan.
Meeting: 2018 American Transplant Congress
Abstract number: A433
Keywords: Tolerance
Session Information
Session Name: Poster Session A: Tolerance / Immune Deviation
Session Type: Poster Session
Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Introduction
Recently, Todo et al. reported that ex-vivo generated immunomodulatory cells induced operational tolerance in 7/10 liver transplanted recipients. To allow wide spread application, it is crucial to address which cells are responsible for the donor-antigen specific immunomodulatory effects.
Methods
Immunomodulatory cells were generated by 14 days co-culture of recipient peripheral blood mononuclear cells (PBMCs) (50 x 10^6 cells) with irradiated HLA-mismatched donor PBMCs (20 x 10^6 cells) in presence of CTLA4-Ig (40 mg/10^6 recipient PBMCs). The generated cells were enriched for CD4+ CD25+ cells (Tregs) using MACS, or depleted of CD4+ or CD8+ (using MACS), CD19+, or CD25+CD127lo (using FACS). Suppressive functions of the non-sorted generated cells, and enriched or depleted cell-populations were measured in vitro: Freshly isolated recipient PBMCs were stimulated by irradiated donor or 3rd party PBMCs, with or without generated cells. Cell proliferation and cytokine production was compared.
Results
Non-sorted cells showed significantly stronger donor antigen-specific immunomodulatory effects compared to Treg enriched cells.
Treg or B-cell depleted generated cells showed immunomodulatory effects against both donor and 3rd party antigen.
Depletion of CD4+ or CD8+ cells maintained the donor-antigen specific inhibitory effects. IFN-γ was mainly produced by CD4+ cells. Depletion of B-cells or Tregs from the generated cells lower the production of IL-10.
Conclusion
The ex-vivo generated cells without any enrichment showed stronger donor antigen-specific immunomodulatory effect. The Tregs and B-cells seems to be important in generating the donor-specificity.
CITATION INFORMATION: Yao M., Kumagai-Braesch M., Watanabe M., Tokodai K., Lundgren T., Uhlin M., Ericzon B. Ex-Vivo Generation of Alloantigen-Specific Immunomodulatory Cells: Elucidating the Mechanistical Synergy of Cell Components Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Yao M, Kumagai-Braesch M, Watanabe M, Tokodai K, Lundgren T, Uhlin M, Ericzon B. Ex-Vivo Generation of Alloantigen-Specific Immunomodulatory Cells: Elucidating the Mechanistical Synergy of Cell Components [abstract]. https://atcmeetingabstracts.com/abstract/ex-vivo-generation-of-alloantigen-specific-immunomodulatory-cells-elucidating-the-mechanistical-synergy-of-cell-components/. Accessed October 11, 2024.« Back to 2018 American Transplant Congress