Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells

Priming of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs) is crucial for elimination of pathogens and malignant cells. To activate CTLs, DCs present antigenic peptide-complexed MHC class I molecules (MHC-I) that will be recognized by the CTLs with T cell receptors and CD8 molecules. Here we show that paired Ig-like receptor (PIR)-B, an MHC-I receptor expressed on antigen-presenting cells, can regulate CTL triggering by blocking the access of CD8 molecules to MHC-I. PIR-B-deficient DCs evoked CTLs more efficiently, leading to accelerated graft and tumor rejection. PIR-B(+) non-DC transfectant cells served as less efficient stimulators and targets for CTLs than PIR-B(-) cells at the effector phase in vitro. On surface plasmon resonance analysis, PIR-B and CD8alpha alpha were revealed to compete in binding to MHC-I. Our results may provide a novel strategy for regulating CTL-mediated immunity and diseases in a sterical manner.     

Comparison of myocardial perfusion by distal protection before and after primary stenting for acute myocardial infarction: angiographic and clinical results of a randomized controlled trial.

OBJECTIVES: To assess the myocardium-reperfusing effect of a distal protection device, GuardWire Plus (GuardWire Plus), in patients with acute myocardial infarction (AMI). BACKGROUND: Distal embolization may result in reduced myocardial perfusion, increasing the risk of non-Q-wave myocardial infarction and death. Distal protection devices may protect the microcirculation from embolic debris, improving short- and long-term clinical outcomes. METHODS: From February 2002 to July 2003, a total of 341 AMI patients at 22 institutions in Japan were enrolled in the present, multicenter, prospective, randomized trial. Patients experiencing AMI within 12 hr of symptom onset, who were considered treatable by stenting and who met the inclusion criteria, were eligible for randomization. Stenting with and without GuardWire Plus was conducted to examine whether the device provides faster and more complete ST-segment resolution, smaller infarct size, and improved myocardial blush score. RESULTS: The rates of slow flow and no-reflow immediately after PCI were 5.3 and 11.4% in the GuardWire Plus and control groups, respectively (P = 0.05). Blush score 3 acquisition rates immediately after PCI were 25.2 and 20.3% in the GuardWire Plus and control groups, respectively (P = 0.26), and the rates at 30 days after PCI were 42.9 and 30.4%, respectively (P = 0.035). CONCLUSIONS: A significant difference was found between the GuardWire Plus and control groups with respect to the total incidence of distal embolization, indicating that GuardWire Plus angiographically improved myocardial perfusion without demonstrating the preventive effect of myocardial damage.     

Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Between the two recognized estrogen receptors (ERs), ER alpha and ER beta, only ER alpha had been detected in murine skin. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.     

Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival

We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus.     

Association of interleukin-10 promoter single nucleotide polymorphisms -819 T/C and -592 A/C with aging

Increased inflammatory activity is known to accompany aging. Single nucleotide polymorphisms of inflammatory mediator genes might therefore affect the aging process. Relation of eight SNPs (tumor necrosis factor-alpha [TNF-alpha] -1031 T/C, interleukin-10 [IL-10] -819 T/C, IL-1beta -511 C/T, IL-6 -634 C/G, IL-18 -607 A/C, transforming growth factor-beta [TGF-beta] +869 C/T, matrix metalloproteinase-1 [MMP-1] -1607 1G/2G, and MMP-3 -1171 5A/6A) with age or gender was evaluated in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) by the chi-square test. There was a significant association of IL-10 -819 T/C with age (p =.0026). The association remained significant after multivariate logistic regression analysis (odds ratio for an age interval for 1 year, 1.009; 95% CI, 1.002-1.016). Furthermore, the genotype distribution of IL-10 -819 T/C was completely consistent with that of -592 A/C. These data suggest that IL-10 -819 T/C and -592 A/C may be a promising candidate for an aging-related gene in a Japanese population.     

Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints

OBJECTIVE: We have reported that articular cartilage showed early stage degeneration at 7 and 14 days after immobilization, moderate degeneration at 28 days, and severe degeneration at 42 days in rabbits. To test whether apoptosis occurs in association with p53 expression in chondrocytes during the process of articular cartilage degeneration, we investigated the degree of cartilage degeneration, the frequency of apoptotic cells, and the levels of p53 mRNA in rabbits and mice after knee immobilization. METHODS: Right knees of male Japanese white rabbits were immobilized in full extension with fiberglass casts for up to 42 days. Similarly, right knees of male p53 wild-type [p53 (+/+)] and p53 null [p53 (-/-)] mice were immobilized in full extension with bandage tape for up to 84 days. Apoptotic cells were confirmed by TUNEL staining on the sections of knee joints. Total RNA of articular chondrocytes obtained from Day 0 or immobilized knees was analyzed semiquantitatively by RT-PCR using specific primers for p53. RESULTS: Articular cartilage degenerated after immobilization of p53 (+/+) mouse knees, but not after immobilization of p53 (-/-) knees. Apoptotic cells were observed in articular cartilage in the femur and tibia of rabbits and p53 (+/+) mice after immobilization. However, only a few apoptotic cells were observed at the same sites in p53 (-/-) mice. In RT-PCR analysis, the levels of p53 mRNA obtained from immobilized groups were significantly higher than those of Day 0 groups in rabbit and p53 (+/+) mouse knees. CONCLUSION: Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints.     

Increased plasma thioredoxin in patients with acute myocardial infarction

BACKGROUND AND HYPOTHESIS: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion. METHODS: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS. RESULTS: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors. CONCLUSION: Plasma thioredoxin levels are elevated in patients with AMI, and higher thioredoxin levels may predict subsequent failed coronary reperfusion therapy in patients with AMI.