Transplant Site Influences the Immune Response After Islet Transplantation: Bone Marrow Versus Liver

Background. The aim of this study was to characterize the immune response against intrabone marrow (BM-Tx) or intraliver (liver-Tx) transplanted islets in the presence or in the absence of immunosuppression. Methods. Less (C57BL/6 in Balb/c) and highly (Balb/c in C57BL/6) stringent major histocompatibility complex fully mismatched mouse models were used to evaluate the alloimmune response. Single antigen-mismatched mouse model (C57BL/6 RIP-GP in C57BL/6) was used to evaluate the antigen-specific immune response.Mice received tacrolimus (FK-506, 0.1mg/kg per day)/mycophenolate mofetil (MMF, 60mg/kg per day), and anti-CD3 (50 ?g/day) either alone or in combination. Results. Transplant site did not impact the timing nor the kinetics of the alloimmune and single antigen-specificmemory Tcell responses in the absence of immunosuppression or in the presence of MMF/FK-506 combination. On the other hand, the median time to graft rejection was 28 ± 5.2 days and 16 ± 2.6 days (P = 0.14) in the presence of anti-CD3 treatment, 50 ± 12.5 days and 10 ± 1.3 days (P = 0.003) in the presence of anti-CD3/ MMF/FK-506 treatment for liver-Tx and BM-Tx, respectively. Anti-CD3 did not differentially reach BM and liver tissues but was more effective in reducing graft associated Tcell responses in liver-Tx than in BM-Tx. Conclusions. Islets infused in the BM appear less protected from the adaptive immune response in the presence of the anti-CD3 treatment. This result raises some concerns over the potential of the BM as a site for islet allotransplantation. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.