TL;DR: It is found that the coinhibitory cell surface receptor programmed death 1 (PD-1) on cytotoxic T cells mediates to their tolerance and this results clarify how the kidney/renal lymph node system tolerizes the immune system against circulating innocuous antigens.
Abstract: Although the spleen is a major site where immune tolerance to circulating innocuous antigens occurs, the kidney also contributes. Circulating antigens smaller than albumin are constitutively filtered and concentrated in the kidney and reach the renal lymph node by lymphatic drainage, where resident dendritic cells (DCs) capture them and induce tolerance of specific cytotoxic T cells through unknown mechanisms. Here, we found that the coinhibitory cell surface receptor programmed death 1 (PD-1) on cytotoxic T cells mediates to their tolerance. Renal lymph node DCs of the CD8(+) XCR1(+) subset, which depend on the transcription factor Batf3, expressed the PD-1 cognate ligand PD-L1. Batf3-dependent DCs in the renal lymph node presented antigen that had been concentrated in the kidney and used PD-L1 to induce apoptosis of cytotoxic T cells. In contrast, T cell tolerance in the spleen was independent of PD-1, PD-L1, and Batf3. In summary, these results clarify how the kidney/renal lymph node system tolerizes the immune system against circulating innocuous antigens.
TL;DR: The incidence and histopathological features of various long‐term developing renal tumors observed in control rats observed in Sprague‐Dawley rats and Fischer‐344 (F‐344) rats are presented.
Abstract: Spontaneous renal neoplasms in the rat are uncommon. This paper presents the incidence and histopathological features of various long-term developing renal tumors observed in control rats from 17 carcinogenicity studies (1340 males and 1329 females) in Sprague-Dawley rats and 10 carcinogenicity studies (530 males and 530 females) in Fischer-344 (F-344) rats. Renal cell adenoma (0.08% in Sprague-Dawley and 0.28% in F-344), lipoma/liposarcoma (0.37% in Sprague-Dawley and 0.75% in F-344) and transitional cell carcinoma (0.07% in Sprague-Dawley and 0.09% in F-344) were observed in both Sprague-Dawley (0.49%) and F-344 (1.13%) rats. Pulmonary metastasis was observed from one case of transitional cell carcinoma. Renal cell carcinoma with metastasis to the lung and liver was seen in one F-344 rat. In addition, transitional cell papilloma and nephroblastomas were also observed in Sprague-Dawley rats. Metastases from nephroblastoma were seen in the lungs and renal lymph node in two cases. In both rat strains, the tumor incidence was higher in males than in females.
TL;DR: Results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs. systemic, immune responses during renal colonization infection.
Abstract: Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM) components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs. systemic, immune responses during renal colonization infection. The use of inbred immunocompetent rats provides a novel tool to further elucidate those pathophysiological pathways that facilitate the unique biological equilibrium observed in reservoir hosts of leptospirosis.
TL;DR: The past decade has seen remarkable progress in understanding of the immunologic responses associated with diseases of the kidney, with many laboratories using animal models to detailed the diversity of bone marrow-derived immune cells present in the kidney during health and disease.
Abstract: The past decade has seen remarkable progress in our understanding of the immunologic responses associated with diseases of the kidney. In particular, the diversity of bone marrow-derived immune cells present in the kidney during health and disease has been detailed by many laboratories using animal
TL;DR: Main gross findings included multifocal to coalescent skin nodules and multiple nodules, mostly cystic, in both kidneys and metastases in the liver, spleen and lung of one dog and in the renal lymph node in another one.
Abstract: Renal cystadenocarcinoma-nodular dermatofibrosis syndrome of German shepherd are described in four 6 to 10-year-old male dogs. Clinical findings included hematuria and urinary retention, progressive weight loss, polydipsia, anorexia, vomiting, and respiratory distress. Several recurrent skin nodules were observed in one of the dogs. Three dogs died spontaneously and one was euthanatized. Main gross findings included multifocal to coalescent skin nodules and multiple nodules, mostly cystic, in both kidneys. Microscopically there was nodular dermatofibrosis in the skin and renal cysts, dysplastic, hyperplastic and neoplastic changes of the renal tubular epithelium. The neoplasms were classified as cystadenoma in one case and cystadenocarcinoma in the other three. There were metastases in the liver, spleen and lung of one dog and in the renal lymph node in another one.