Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells.

Dendritic cells (DCs) are believed to regulate T cell-mediated immunity primarily by directing differentiation of naive T cells. Here, we show that a large fraction of CD4(+) memory cells produce IL-10 within the first hours after interaction with plasmacytoid DCs (PDCs). In contrast, CD11c(+) DCs induce IFN-gamma and little IL-10.

ALS: cytokine profile in cerebrospinal fluid T-cell clones.

T -cells are present in the spinal cord from patients with amyotrophic lateral sclerosis (ALS), and could attack neurons or activate microglia through secretion of cytokines. We report that interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5 and IL-10 could not be detected in cerebrospinal fluid (CSF) samples from 15 ALS patients and 23 out of 25 controls with a multiplexed cytometric bead assay. In vivo activated T-cell clones were established from CSF (n = 26) and blood (n = 21) of one ALS patient.

CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection.

It has been suggested that human cytomegalovirus (HCMV) evades the immune system by infecting and paralyzing antigen-presenting cells. This view is based mainly on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy persons, indicating that other key antigen-presenting cells induce an efficient immune response.

Cerebrospinal fluid CD4+ T cells from a multiple sclerosis patient cross-recognize Epstein-Barr virus and myelin basic protein.

Epstein-Barr virus-specific CD4+ T cells could be involved in the pathogenesis of multiple sclerosis, provided they can gain entry to the intrathecal compartment. The authors have previously demonstrated that cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus-transformed B cells. They now report that CD4+ T cells specific for the Epstein-Barr virus DNA polymerase peptide EBV 627-641 were present in the cerebrospinal fluid from one of two multiple sclerosis patients, and that a high proportion of these CD4+ T cells cross-recognized an immunodominant myelin basic protein peptide, MBP 85-99.

Plasmacytoid dendritic cells activate allergen-specific TH2 memory cells: modulation by CpG oligodeoxynucleotides.

Background: Plasmacytoid dendritic cells (PDCs) accumulate in the nasal mucosa of allergic rhinitis patients, but their function in upper airway allergy has not been determined. CpG oligodeoxynucleotides, potent adjuvants in immunotherapeutic strategies in animal models, are especially effective at activating PDCs. These cells are therefore potential targets for immunomodulation in humans.

EUK-134 reduces renal dysfunction and injury caused by oxidative and nitrosative stress of the kidney.

Background/aims: Oxidative and nitrosative stress plays important roles in the pathogenesis of renal ischemia/reperfusion (I/R) injury. Here we investigate the effect of EUK-134, a synthetic superoxide dismutase and catalase mimetic, (i) on renal dysfunction and injury caused by I/R in vivo and (ii) on proximal tubular cell (PTC) injury and death caused by oxidative and nitrosative stress.

Methods: Rats, subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h), were administered EUK-134 (0.

The tyrosine kinase inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat.

Background: We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney.

Methods: Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal dysfunction and injury were measured and renal sections assessed for renal injury.

GW274150 inhibits nitric oxide production by primary cultures of rat proximal tubular cells.

Background: Production of nitric oxide (NO) subsequent to expression of inducible NO synthase (iNOS) contributes to the development of ischemic renal injury and inflammation. Here we investigate the effects of GW274150, a potent, long-acting and highly selective inhibitor of iNOS activity, on NO production by primary cultures of rat proximal tubular cells (PTC).

Material/methods: Pure populations of PTC were isolated from the cortex of kidneys obtained from male Wistar rats using a combination of collagenase digestion, sieving and Percoll centrifugation.

High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury.

High-density lipoproteins (HDL) have been shown to reduce organ injury and mortality in animal models of shock via modulation of the expression of adhesion molecules and pro-inflammatory enzymes. As renal inflammation plays an important role in the development of ischemia/reperfusion (I/R) injury of the kidney, the aim of this study was to investigate the ability of HDL to alleviate renal dysfunction and injury in a rat model of renal I/R. HDL (80 mg/kg, intravenous) was administered to male Wistar rats 30 min before bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h.

GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury.

Background: Generation of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) may contribute to renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of GW274150, a novel, highly selective, potent and long-acting inhibitor of iNOS activity in rat and mouse models of renal I/R.

Methods: Rats were administered GW274150 (5 mg/kg intravenous bolus administered 30 minutes prior to I/R) and subjected to bilateral renal ischemia (45 minutes) followed by reperfusion (6 hours).

Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury.

Background: Nitric oxide (NO), produced via inducible nitric oxide synthase (iNOS), is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of the iNOS inhibitors L-N6-(1-iminoethyl)lysine (L-NIL) and aminoethyl-isothiourea (AE-ITU) on (a) renal dysfunction and injury mediated by bilateral I/R of rat kidneys in vivo and (b) cytokine-stimulated NO production by primary cultures of rat proximal tubule (PT) cells.

Methods: Male Wistar rats subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h).