Author(s): Kerjaschki D, Regele HM, Moosberger I, NagyBojarski K, Watschinger B,
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Abstract Renal transplant rejection is caused by a lymphocyte-rich inflammatory infiltrate that attacks cortical tubules and endothelial cells. Immunosuppressive therapy reduces the number of infiltrating cells; however, their exit routes are not known. Here a >50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human renal transplant biopsies using antibodies to the lymphatic endothelial marker protein podoplanin. Nodular infiltrates are constantly associated with newly formed, Ki-67-expressing lymphatic vessels and contain the entire repertoire of T and B lymphocytes to provide specific cellular and humoral alloantigenic immune responses, including Ki-67(+) CD4(+) and CD8(+) T lymphocytes, S100(+) dendritic cells, and Ki-67(+)CD20(+) B lymphocytes and lambda- and kappa-chain-expressing plasmacytoid cells. Numerous chemokine receptor CCR7(+) cells within the nodular infiltrates seemed to be attracted by secondary lymphatic chemokine (SLC/CCL21) that is produced and released by lymphatic endothelial cells in a complex with podoplanin. From these results, it is speculated that lymphatic neoangiogenesis not only contributes to the export of the rejection infiltrate but also is involved in the maintenance of a potentially detrimental alloreactive immune response in renal transplants and provides a novel therapeutic target.
This article was published in J Am Soc Nephrol
and referenced in Journal of Clinical & Cellular Immunology