A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes.

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+ pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+ progenitors. These CD2hiCD5+CD81+ cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5+CD81+ pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5-CD81- pDCs, human CD5+CD81+ pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.

Application of machine perfusion preservation as a viability test for marginal kidney graft.

BACKGROUND: This study evaluated the usefulness of machine perfusion preservation parameters as indicators of kidney graft viability. METHODS: Eighty-eight cadaveric kidneys were analyzed in this study. Of these, 74 kidneys (84.1%) were procured from nonheartbeating donors. The criteria for an acceptable kidney for transplantation were a perfusion flow of more than 0.4 mL/min/g with a concurrent decreasing perfusion pressure. The average perfusion pressure was 30-50 mmHg. We divided the kidneys into three groups: group 1 (n=35), 0.45-0.65 mL/min/g machine perfusion flow (MPF); group 2 (n=30), 0.65-0.90 mL/min/g MPF; and group 3 (n=23), more than 0.9 mL/min/g MPF. RESULTS: A higher rate of primary nonfunction (PNF; 25.7%) was found in group 1, compared with 6.7% in group 2 and 0% in group 3. A higher rate of 30.4% immediate function was found in group 3, compared with 16.7% in group and 8.6% in group 1. However, a longer period of acute tubular necrosis (ATN; 12.0 days) was found in group 1 compared with 8.6 days in group 2 and 8.7 days in group 3. PNF was detected in 7 (77.8%) cases with more than 16 hr of total ischemic time (TIT) in group 1. In contrast, all of nine cases with more than 16 hr of TIT in group 3 were functional. CONCLUSIONS: MPF is a reliable indicator of graft viability based on the rate of PNF and immediate renal allograft function, especially in marginal donors.

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Repeated intervenous calcitriol administration is an established treatment for renal osteodystrophy. However, the therapeutic effects of this treatment vary among patients, and it cannot be administered to patients with hypercalcemia. This time, we investigated the relationship between dialysate dose and the effects of intervenous calcitriol administration. The results demonstrated that normal-calcium dose dialysate is more useful than low-calcium dose dialysate.

Lymphocyte drug sensitivity is useful for prediction of the antiproteinuric effect and relapse rate in cyclosporine treatment for frequent-relapse minimal change nephrotic syndrome.

BACKGROUND/AIMS: The therapeutic effect of cyclosporine A (CsA) in combination with steroids varies greatly for frequent-relapse minimal change nephrotic syndrome (FRMCNS). The association between the sensitivity of peripheral blood lymphocytes (PBLs) to CsA in vitro and the therapeutic effect of CsA in FRMCNS were investigated. METHODS: The sensitivity of PBLs in vitro and the therapeutic effect of CsA in 23 FRMCNS patients were compared. The length of time to complete remission (CR) and the number of relapses were compared using the 50% inhibitory concentration (IC(50)) of CsA in the presence of a T-cell mitogen. RESULTS: FRMCNS patients were divided into 2 groups: a low sensitivity group with an IC(50) of >14.8 ng/ml (GII, n = 10), and a high sensitivity group with an IC(50) of <14.8 ng/ml (GI, n = 13). Comparison of the length of time to CR between the 2 groups showed that GI reached CR earlier than GII (p < 0.01). GI had significantly fewer relapses than GII when CsA was administered for 12 months or longer (p < 0.01). CONCLUSION: Lymphocyte sensitivity to CsA has the potential to be an important clinical indicator of the antiproteinuric effect and relapse rate in FRMCNS.