title: Transplant Site Influences the Immune Response After Islet Transplantation: Bone Marrow Versus Liver.
abstract: 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.
  
  
  
  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, 0.1 mg/kg per day)/mycophenolate mofetil (MMF, 60 mg/kg per day), and anti-CD3 (50 μg/day) either alone or in combination.
  
  
  
  Transplant site did not impact the timing nor the kinetics of the alloimmune and single antigen-specific memory T cell 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 T cell responses in liver-Tx than in BM-Tx.
  
  
  
  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.
authors: 1 Division of Immunology, Transplantation and Infectious Diseases, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2 Lymphocyte Activation Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors: Elisa
authors: E
authors: Cantarelli
authors: Antonio
authors: A
authors: Citro
authors: Silvia
authors: S
authors: Pellegrini
authors: Alessia
authors: A
authors: Mercalli
authors: Raffaella
authors: R
authors: Melzi
authors: Erica
authors: E
authors: Dugnani
authors: Tatiana
authors: T
authors: Jofra
authors: Georgia
authors: G
authors: Fousteri
authors: Anna
authors: A
authors: Mondino
authors: Lorenzo
authors: L
authors: Piemonti
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000601:surgery*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D007518:Isoantibodies / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D007519:Isoantigens