Donor-Specific Tregs Prolong Peripheral Chimerism in Baboons Receiving GalTKO hCD47-tg Porcine Peripheral Blood Stem Cells

N. P. Llore¹, J. Stern¹, G. Pierre¹, E. Lopes¹, D. Ekanayake-Alper¹, P. Alonso-Guallart¹, K. Bruestle¹, H. Sakai¹, D. Ayares², M. Lorber², R. Hawley¹, D. H. Sachs¹, M. Sykes¹, A. D. Griesemer¹

¹Columbia Center for Translational Immunology, New York, NY, ²United Therapeutics, Silver Springs, MD

Meeting: 2019 American Transplant Congress

Abstract number: D79

Keywords: Bone marrow transplantation, Mixed chimerism, Pig, Stem cells

Session Information

Session Name: Poster Session D: Xenotransplantation

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: We have previously evaluated the ability of transplantation of polyclonal expanded recipient T regulatory cells to prolong xenogeneic chimerism and skin grafts after transplantation of mobilized GalTKO/ hCD46/ hCD47 pig PBSCs to baboon recipients. Here, we study whether the administration of donor-specific expanded Tregs can further prolong macrochimerism following mobilized pig peripheral blood stem cell (PBSC) transplantation.

*Methods: Eight P. hamadryas received a non-myeloablative preconditioning regimen consisting of total body irradiation, thymic irradiation, rituximab, ATG, anti-CD154 mab, anti-CD2 antibody and sirolimus. Group 1 animals (n=2) received GalTKO/ hCD46/ hCD47 pig PBSC only, Group 2 (n=4) received polyclonal Tregs and GalTKO/ hCD46/ hCD47 pig PBSC and Group 3 (n=2) received donor-specific Tregs and GalTKO/ hCD55/ hCD47 PBSC. Peripheral blood and bone marrow chimerism were detected by flow cytometry using pan-pig and anti-swine CD45 mAb. Anti-pig responses were detected by mixed lymphocyte reaction (MLR) and anti-donor serum antibody levels.

*Results: Macrochimerism was higher in the first 24 hours after infusion in the group of baboons that received regulatory T cells vs Group 1 (Figure 1). In addition, peripheral macrochimerism was detectable for sixteen days in baboons receiving donor-specific Treg infusions and GalTKO/hCD55/hCD47 PBSC, showing considerable prolongation compared to baboons that received polyclonal Tregs and GalTKO/hCD46/CD47 PBSC, where chimerism was only detectable for 24 hours (Figure 2).

*Conclusions: Recipients of donor-specific Tregs plus GalTKO/hCD55/hCD47 PBSC had prolonged xenogeneic chimerism compared to recipients of GalTKO/hCD46/hCD47 PBSC with or without polyclonal Tregs. This is likely due to the increased suppression associated with donor-specific Tregs compared to polyclonal Tregs, although additional controls are needed to rule out a contribution of hCD55 (compared to hCD46) in prolongation of chimerism.

To cite this abstract in AMA style:

Llore NP, Stern J, Pierre G, Lopes E, Ekanayake-Alper D, Alonso-Guallart P, Bruestle K, Sakai H, Ayares D, Lorber M, Hawley R, Sachs DH, Sykes M, Griesemer AD. Donor-Specific Tregs Prolong Peripheral Chimerism in Baboons Receiving GalTKO hCD47-tg Porcine Peripheral Blood Stem Cells [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-specific-tregs-prolong-peripheral-chimerism-in-baboons-receiving-galtko-hcd47-tg-porcine-peripheral-blood-stem-cells/. Accessed November 21, 2024.

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