title: Effect of Absent Immune Cell Expression of Vitamin D Receptor on Cardiac Allograft Survival in Mice.
abstract: BACKGROUND
  Vitamin D (VD) has immunomodulatory properties, but whether immune cell expression of the VD receptor (VDR) impacts costimulatory blockade induced cardiac allograft survival is not known.
  
  
  METHODS
  To localize effects of VDR deficiency to hematopoietic cells and to avoid the metabolic consequences of systemic VDR deficiency, we produced bone marrow (BM)-chimeric mice by transplanting lethally irradiated C57BL/6 mice with congenic VDR or wild type BM. After reconstitution, we characterized baseline immune profiles and transplanted chimeras with heterotopic cardiac allografts with or without costimulatory blockade using anti-CD154 (MR1) or CTLA4Ig, the latter approved for use in human kidney transplant recipients.
  
  
  RESULTS
  Immune reconstitution occurred equivalently in chimeras with wild type and VDR BM. Untreated animals rejected class II disparate and fully allogeneic cardiac transplants with similar kinetics. Compared to untreated controls, treatment with either MR1 or CTLA4Ig induced significant and equivalent prolongation of graft survival in both groups of chimeric recipients. We observed no differences in induced antidonor cellular or humoral alloimmunity between groups.
  
  
  CONCLUSIONS
  Our findings support the conclusion that absent immune cell VDR expression (a) does not impact the strength, phenotype, or kinetics of heart transplant rejection in mice and (b) does not impact the graft-prolonging effects of costimulatory blockade including that induced by clinically used CTLA4Ig.
authors.affiliation: 1 Translational Transplant Research Center, Division of Nephrology, Department of Medicine, The Immunology Institute, and Recanati-Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York NY.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Gavzy
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000069594:Abatacept / Q000494:pharmacology; D064591:Allografts; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D023201:CD40 Ligand / Q000037:antagonists & inhibitors / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D018183:Transplantation Chimera; D014916:Whole-Body Irradiation
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D018167:Receptors, Calcitriol; D023201:CD40 Ligand; D000069594:Abatacept