Lymphatic Neoangiogenesis in Human Kidney Transplants Is Associated with Immunologically Active Lymphocytic Infiltrates

Abstract

Abstract. Renal transplant rejection is caused by a lymphocyterich 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 Ͼ50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human renal transplant biopsie susing 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 ϩ CD4 ϩ and CD8 ϩ

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

“…As previously described by Kerjaschki et al (2004) in transplanted kidneys, we found nodular cellular infiltrates within the regions of higher LV count. To further characterize the infiltrating cell populations, IHC stainings for B lymphocytes, that is, CD20 for B cells and CD27 for plasma cells, were performed.…”

“…Most data about renal lymphangiogenesis have so far been obtained in kidney transplant recipients with either acute graft rejection or chronic allograft nephropathy (Kerjaschki et al, 2004;Adair et al, 2007;Stuht et al, 2007). In both cases, the number of lymph vessels was much higher when compared with native nephrectomy tissue; however, there was no significant difference in LV density between different Banff rejection grades and chronic allograft nephropathy (Stuht et al, 2007).…”

“…This uncertainty is reflected in the ongoing post-transplant discussion on whether increased LVD in the kidney allograft predicts a higher risk of organ loss or a better graft survival. Both an ongoing maintenance of immune response through lymphocyte invasion and a clearing function of infiltrates can be attributed to lymph vessels (Kerjaschki et al, 2004). Thus, neolymphangiogenesis could be detrimental if the immune process is perpetuated and augmented in the inflammed tissues, but it may be beneficial if cytotoxic cells are removed more efficiently.…”

“…Lymph vessels originate from embryonic veins, and except for the eye and the brain, they can be found physiologically in several organs as a characteristic feature of higher vertebrates. This ''second circulation'' network is also present in the kidney, where the lymph vessels are confined to the area around largeand middle-sized arteries (McIntosh and Morris, 1971) in the cortex, but do not appear in the peritubular space (Kerjaschki et al, 2004). The medulla of a healthy person rarely possesses any lymphatics (Cuttino et al, 1989).…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…Adult lymphangiogenesis occurs during inflammation and wound healing [1,10], but is also strongly associated with chronic inflammation, autoimmunity, and allograft rejection [11][12][13][14][15][16] as well as with tumor invasion and metastasis when initiated both around the tumor and in the draining LN [17][18][19][20][21]. These are all associated with different immunological outcomes: from Th1 and Th2 inflammatory responses to immune escape and tolerance.…”