Effect of Absent Immune Cell Expression of Vitamin D Receptor on Cardiac Allograft Survival in Mice.

INTRODUCTION: 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.