Recent evidence fromseveral groups indicates that IL‐17‐producing Th17 cells, rather than, as once was thought, IFN‐γ‐producing Th1 cells, can represent the key effector cells in the ...induction/development of several autoimmune and allergic disorders. Although Th17 cells exhibit certain phenotypic and developmental differences from Th1 cells, the extent of the differences between these two T cell subsets is still not fully understood. We found that the expression profile of cell surface molecules on Th17 cells has more similarities to that of Th1 cells than Th2 cells. However, although certain Th1‐lineage markers i.e., IL‐18 receptor α, CXCR3, and T cell Ig domain, mucin‐like domain‐3 (TIM‐3), but not Th2‐lineage markers (i.e., T1/ST2, TIM‐1, and TIM‐2), were expressed on Th17 cells, the intensity of expression was different between Th17 and Th1 cells. Moreover, the expression of CTLA‐1, ICOS, programmed death ligand 1, CD153, Fas, and TNF‐related activation‐induced cytokine was greater on Th17 cells than on Th1 cells. We found that IL‐23 or IL‐17 can suppress Th1 cell differentiation in the presence of exogenous IL‐12 in vitro. We also confirmed that IL‐12 or IFN‐γ can negatively regulate Th17 cell differentiation. However, these cytokines could not modulate such effects on T cell differentiation in the absence of APC.
The TWEAK/Fn14 axis in anaphylactic shock Galli, Stephen J.
Journal of allergy and clinical immunology,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
145, Številka:
2
Journal Article
Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This ‘bad side’ of mast cells and IgE is so well accepted that it can be difficult ...to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as “misdirected” type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.
Unfortunately, skin-resident mast cells are difficult to isolate, and work with such cells would help discriminate direct from indirect effects of anti-FcεRI autoantibodies on mast cells. ......experiments using cord blood–or CD34+-derived mast cells (which do not share all of the functional characteristics of tissue-resident mast cells) can yield results that depend importantly on the functional properties of mast cells generated in vitro but might not apply to those mast cells found in real environments occupied in vivo. ...in his study MacGlashan6 used an upper limit of 25% serum in assessing samples, reflecting the needs of the autoanalyzer for the histamine used. ...although the results were few and presented cautiously, in the 3 instances in which “positive” sera were tested with sera obtained a year or more later, the positive results were not repeated.
IgE-mediated activation of mast cells is a hallmark of an anaphylactic reaction to allergen. In this issue of the JCI, Duan et al. describe an approach for suppressing IgE-dependent mast cell ...activation, thereby suppressing anaphylaxis. Specifically, the authors show that delivery of liposomes containing both the specific antigen recognized by the mast cell-bound IgE and a high-affinity glycan ligand of the inhibitory receptor CD33 (CD33L) to targeted mast cells inhibits antigen-induced, FcεRI-dependent spleen tyrosine kinase (Syk) phosphorylation and downstream protein tyrosine kinase (PTK) phosphorylation, Ca++ flux, and β-hexosaminidase release (i.e., degranulation). However, this strategy only worked if both the antigen (reactive with the mast cell-bound IgE) and CD33L were on the same liposome. This approach promises to rapidly reduce IgE-dependent mast cell activation in response to challenge with offending allergens.
Background The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of ...operationally defined clinical tolerance. Objective Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. Methods In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13). Results Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells. Conclusion In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.
Background Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature ...and time of storage before testing, complicating comparisons of results from various studies. Objective We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample. Methods Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs. Results Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63hi population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63hi basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C. Conclusion BATs to measure upregulation of basophil CD203c and induction of a CD63hi basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.
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