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Expression of rectoptor activator of nuclear factor – kappa B ligand and its receptor is associated with T lymphocytes in acute kidney rejection

A cross talk between bone metabolism and immune system, known as osteoimmunology, indicates the importance of receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) activities. RANKL is an osteoclastogenic cytokine and a participant in physiological and pathological bone resorption. Except bone, inflammatory response is different tissue is also a source of the molecules. T lymphocytes produce RANKL in its soluble form. When produced in tissue RANKL binds to RANK expression on macrophage – monocyte and dendritic cell regulating their function. Transplanted kidney is place of host versus graft response with strong lymphocyte infiltration. Production of different cytokines results in defected parenchyma function and organ rejection. Our study aimed associating RANK/RANKL with T cell infiltration in kidney tissue of acutely rejected transplantat. These activated T cell lymphocytes may be the source of serum elevated sRANKL during post transplantation period and responsible for continuing bone resorption. We performed kidney transplantation on 15 rats using Wistar as recipients and DA as donors. Transplanted kidneys were harvested 21 days following transplantation, during that time animals received no immunosuppressive treatment. Tissue sections were analyzed to identify colocalization of CD4+, CD8+, CD45+, CD68+ lymphocytes and RANKL+, RANK+ cell immunoreactions by immunofluorescent microscopy. CD4+ lymphocytes were the predominant infiltrate cell subset present in acutely rejected kidney tissue. On surface of CD4+ and CD8+ cells granular RANKL immunoreactivity was detected. Highest RANKL expression and intensity was observed in CD4+ lymphocytes. On CD68 positive cells only RANK was detected as surface staining. CD45 lymphocytes showed no RANK or RANKL immunoreactivity. These data demonstrated that CD4+ T cells are the main cell responsible for higher levels of RANKL observed in rejected kidney tissue.

kidney transplantation; rejection; RANKL; RANK

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