T-cell reactivity to Cor a 8 is predominantly based on cross-reactivity with Pru p 3, indicating that the latter initiates sensitisation to its homolog in hazelnut. The limited allergenic potential of Cor a 8 seems to be associated with rapid lysosomal degradation during allergen processing and the lack of major T-cell-activating regions.

BackgroundTo avert the differentiation of allergen-specific Th2 cells in atopic individuals is a major goal in the prevention and therapy of IgE-mediated allergy. We aimed to compare different toll-like receptor (TLR) agonists regarding their effects on antigen-presenting cells and the differentiation of naïve T cells from allergic patients.MethodsMonocytes and monocyte-derived dendritic cells (mdDC) from allergic patients were stimulated with Pam3CSK4 (TLR1/2 ligand), FSL-1 (TLR2/6 ligand), monophosphoryl lipid (MPL)-A, lipopolysaccharide (LPS, both TLR4 ligands), and flagellin (TLR5 ligand). Allergen uptake and upregulation of CD40, CD80, CD83, CD86, CD58, CCR7 and PD-L1 were analyzed by flow cytometry. Functional maturation of mdDC was tested in mixed leukocyte reactions, and the synthesis of proinflammatory cytokines, IL-10 and members of the IL-12 family was assessed. TLR-ligand-activated mdDC were used to stimulate naïve CD4+ T cells, and cytokine responses were assessed in supernatants and intracellularly.ResultsAll TLR ligands except flagellin enhanced allergen uptake. All TLR ligands induced functional maturation of mdDC with differential expression of surface molecules and cytokines and promoted the differentiation of IFN-γ-producing T cells. LPS-matured mdDC exclusively induced Th1-like responses, whereas mdDC stimulated with the other TLR ligands induced both Th1- and Th0-like cells. Pam3CSK4 and flagellin additionally induced Th2-like cells. Th1-like responses were associated with higher expression levels of co-stimulatory molecules, PD-L1, IL-6, TNF-α, and IL-12p70. None of the TLR-ligand-stimulated mdDC induced IL-10- or IL-17-producing T cells.ConclusionDifferent TLR ligands differently influence T-cell responses due to varying activation of the three signals relevant for T-cell activation, that is, antigen presentation, co-stimulation and cytokine milieu.

Originally limited to basophils and mast cells, the spectrum of high affinity IgE receptor (Fc epsilon RI-bearing cells has expanded recently to include Langerhans cells, dermal dendritic cells (DC), monocytes, and eosinophils. As a result of studies on the distribution, structure, and function of Fc epsilon RI on APCs, we discovered a minor nonbasophil, nonmonocyte PBMC population that can bind IgE via Fc epsilon RI. This receptor occurs on the surface of these cells as a multimeric structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but, unlike its counterpart on basophils, lacking Fc epsilon RI beta. Further experiments revealed that these Fc epsilon RI alpha gamma-expressing cells closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh; CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low, CD64low) and cell morphology. These features allowed us to isolate Fc epsilon RI-expressing DC from the peripheral blood and to investigate their immunostimulatory properties. We found Fc epsilon RI-positive DC to be efficient stimulators of both primary (allogeneic MLR) and Fc epsilon RI/IgE-dependent, secondary T cell responses at low cell numbers. Thus, Fc epsilon RI-expressing DC may not only amplify established type I allergic immune reactions but, unlike Fc epsilon RI-positive semiprofessional APCs, may be able to prime naive T cells to common and/or cryptic epitopes of IgE-reactive Ags.

Research DigestSlow-release morphine was not more effective than methadone in reducing neonatal abstinence syndrome QUESTION In pregnant women who are opioid dependent or polysubstance abusers, is slow-release morphine with an intermediate half-life (16 hours) more effective than methadone in reducing the neonatal abstinence syndrome in their newborn infants? DESIGNA randomized, unblinded, controlled trial with a mean follow-up of 15 weeks (follow-up information supplied by author). SETTINGA drug addiction outpatient clinic at a university hospital in Vienna, Austria. PARTICIPANTSA total of 48 pregnant women (mean age, 26 years; mean gestation, 22 weeks) who were dependent on opioids or abused polysubstances (mean duration, 61 months) were willing to follow the maintenance program and to avoid using illegal drugs. Follow-up was complete. INTERVENTIONWomen were allocated to receive oral slow-release morphine tablets twice a day (n=24) or an oral methadone solution once a day (n=24). A flexible-dose regimen was used, and the mean dose at delivery was 53 mg for methadone and 300 mg for slow-release morphine. All women received psychosocial counseling twice a week and group psychotherapy once a week. MAIN OUTCOME MEASURESNeonatal abstinence syndrome was assessed every 6 hours using the Finnegan score. Other outcomes were illegal drug consumption (assessed by urinalysis and new injection sites), nicotine dependence (Fagerström questionnaire), and fetal distress. MAIN RESULTS AND CONCLUSIONSNeonatal infants born to mothers in the group receiving methadone and the group receiving slow-release morphine did not differ in the duration of the neonatal abstinence syndrome (16 days in the methadone group vs 21 days in the slow-release morphine group; P=0.18). The women's mean daily dose of slow-release morphine or methadone was not associated with the duration of neonatal abstinence syndrome (r=0.53, and P=0.20 for methadone; r=0.39, and P=0.34 for slow-release morphine). More women in the methadone group than in the slow-release morphine group used additional opiates (P<0.05) (table) and benzodiazepines (P<0.05). Nicotine dependence at delivery decreased from baseline levels in both groups (mean score difference, 11.7 (P=0.02) for methadone, and 16.1 (P=0.02) for slow-release morphine). All women, except 1 who had amniotic rupture, were delivered of their infant during the last trimester (mean gestation, 38 weeks). All neonates were healthy. In pregnant women who were dependent on opiates or who abused polysubstances, slow-release morphine of intermediate-length half-life did not reduce the neonatal abstinence syndrome more than methadone did. Women who received slowrelease morphine used fewer additional opiates and benzodiazepines than women who received methadone. Slow release morphine (SRM) vs methadone in pregnant womenwho were opiate dependent Outcome SRM Methadone RRR (95% CI) NNT (CI) Used additional opiates 21% 50% 58% (6-83) 4 (2-54) RRR = relative risk reduction; NNT = number needed to treat.A recent survey in the ...

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