No abstract

The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8 ؉ T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligandtransduced RMA was rejected, in which CD8 ؉ T cells and NK cells played an essential role. Importantly, CD8 ؉ memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8␣ ؉ , rather than CD8␣ ؊ , dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8␣ ؉ DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligandtransduced RMA was canceled in CD4 ؉ T-cell-depleted and major histocompat- IntroductionImmune surveillance is mediated by both cellular and humoral immunities. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are major players in cell-mediated immunity against tumors or virus-infected cells. CTLs and NK cells often share adhesion or costimulatory molecules, including CD2 and leukocyte function-associated antigen-1 (LFA-1; CD11a/CD18), CD27, 2B4, CD28, inducible costimulator (ICOS), NKG2D, and others. 1,2 These cell-surface molecules not only mediate intercellular binding between these cytotoxic lymphocytes and target cells, but they also participate in signal transduction for cytotoxicity and cytokine secretion. 1,3 DNAM-1 (CD226) is an adhesion molecule that is a member of the immunoglobulin superfamily containing 2 immunoglobulinlike domains of the V-set. 4-6 DNAM-1 is an approximate 65-kDa glycoprotein expressed on the majority of NK cells, T cells, monocytes, and platelets and a subset of B lymphocytes. 4,7,8 The monoclonal antibody (mAb) against DNAM-1 inhibited antigenspecific CTL-mediated and NK-cell-mediated cytolysis of some, but not all, tumor targets in vitro, suggesting that DNAM-1 is involved in cytotoxicity against certain tumor cells expressing the DNAM-1 ligand. Recently, we and others identified the poliovirus receptor (PVR) CD155 and its family member CD112 (PVRrelated family 2 [PRR-2], also called as nectin-2), as the ligands for human DNAM-1. 9,10 Ectopic expression of human CD155 or CD112 rendered tumor cell lines more susceptible to interleukin 2 (IL-2)-activated T and NK-cell-mediated cytotoxicity in vitro. Although the human DNAM-1 ligands CD112 and CD155 are broadly distributed on epithelial and endothelial cells in many tissues, 11,12 they are overexpressed on certain human tumors, including colorectal carcinomas, 13 myeloid leukemias, 14 and neuroblastomas, 15 suggesting that the expression of DNAM-1 ligands is inducible by "stress" such as transformation and infection. However, it has still been an open question how the interaction of DNAM-1 with its ligands is involved in immune responses in vivo.We recently identified the murine homologues of DNAM-1 and its ligands. 16 In the present study, we investigated an in vivo role of DNAM-1 and DNAM-1 ligands on tumor immunosurveillance. Ma...

Abbreviations ACEI Angiotensin converting enzyme inhibitor AKI Acute kidney injury ARB Angiotensin receptor blocker BMI Body mass index BP Blood pressure CCB Calcium channel blocker CKD Chronic kidney disease CVD Cardiovascular disease eGFR Estimated glomerular filtration rate ESKD End-stage kidney disease MRB Mineralocorticoid receptor blocker QOL Quality of life RAS Renin angiotensin system Levels of evidence A High: We are confident that the true effect lies close to that of the estimate of the effect. B Moderate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. C Low: The true effect may be substantially different from the estimate of the effect. D Very low: The estimate of the effect is very uncertain and might often be far from the true effect. None Grade of recommendation 1 "We recommend" 2 "We suggest" None Chapter 1. Diagnosis and definition of chronic kidney disease CQ1-1: How can we diagnose CKD? Statement: CKD is defined as the presence of either of the conditions listed below lasting for more than 3 months. (Level: None, Grade: 1) (1) Findings suggesting kidney damage, i.e., abnormal findings in blood or urinary tests, imaging studies or pathological evaluations. In particular, evidence of proteinuria ≥ 0.15 g/gCr (albuminuria ≥ 30 mg/gCr) is important. (2) GFR < 60 mL/min/1.73 m 2 In clinical practice, eGFR is calculated by the following GFR equation adjusted for the Japanese: eGFR (mL/min/1.73 m 2) = 194 x Cr-1.094 x Age-0.287 (x 0.739 if female) Note: We recommend that serum creatinine (Cr) value (mg/dL) should be evaluated by the enzymatic assay method and rounded off to 2 decimal places. The Japanese GFR equation is applicable to adults aged 18 years or older. CQ 1-2: How can we evaluate the severity of CKD? Statement: We recommend that CKD severity should be evaluated by cause, GFR category, and degree of proteinuria/ Japanese Society of Nephrology published Evidence-based Clinical Practice Guidelines for CKD 2018 (in Japanese) in the Journal of Japanese Society of Nephrology (in press). This is the English digest version of the above guidelines.

Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8 + T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-γ after coculture with allogeneic splenocytes than WT CD8 + T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti-DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD. costimulation | bone marrow transplant