title: Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs.
abstract: BACKGROUND
  Mixed chimerism is associated with donor-specific tolerance. Spleen or splenocyte allotransplantation (Tx) is recognized as potentially tolerogenic. There is no definitive report comparing chimerism levels following spleen and splenocyte Tx in a large animal model. We have compared chimerism after spleen, splenocyte, or kidney Tx in pigs.
  
  
  METHODS
  Outbred (n = 5) and MHC-defined miniature (n = 1) pigs underwent orthotopic spleen Tx. Outbred pigs received splenocytes through a systemic vein (n = 1) or the portal vein (n = 3). Kidney Tx (n = 2) or concomitant Tx of spleen+kidney (n = 2) was carried out. All except one recipient pigs were irradiated (700 cGy thymic and 100-125 cGy whole body) on day-2. Cyclosporine or tacrolimus was administered for 42 days. All donors were males and all recipients were females; chimerism in the blood was determined by Quantification-PCR for the donor Y chromosome. Mixed lymphocyte reaction (MLR) was performed before and after Tx.
  
  
  RESULTS
  One week after spleen Tx in outbred and MHC-defined pigs, chimerism ranged between 0.8 and 22.5%, and 5.4-20.1%, respectively, and remained between 17.7 and 67.4%, and 2.2-7.4%, respectively, until day 28. One week after splenocyte Tx, chimerism ranged between 0.1 and 8.5%, and decreased to 0.1-0.8% at 3-4 weeks. There was no detectable chimerism 14 days after kidney Tx. The response on MLR of all recipient pigs to donor cells was decreased after Tx, except in one case of splenocyte Tx, indicating that this pig might have become sensitized. After discontinuation of immunosuppression, most isolated spleen or kidney grafts were not rejected, but the kidney was rejected after concomitant spleen+kidney Tx.
  
  
  CONCLUSIONS
  There was a significantly higher level of blood chimerism following spleen Tx compared to splenocyte or kidney Tx. However, concomitant Tx of spleen+kidney may be associated with accelerated kidney graft rejection.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Yih Jyh
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Hao-Chih
authors.initials: HC
authors.lastname: Tai
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Mubina A
authors.initials: MA
authors.lastname: Quader
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Houser
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address: cooperdk@upmc.edu.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D046528:Chimerism; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D011839:Radiation, Ionizing; D013154:Spleen / Q000276:immunology* / Q000637:transplantation; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000008:administration & dosage; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D006649:Histocompatibility Antigens; D016572:Cyclosporine; D016559:Tacrolimus
keywords: Hematopoietic cell chimerism; Pig; Splenocyte; Transplantation, kidney; Transplantation, spleen