Two Distinct T Cell Subsets, CD4+ and CD8+CD60+, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses

Smith‐Norowitz, Tamar A.; Silverberg, Jonathan I.; Norowitz, Kevin B.; Bluth, Martin H.; Chice, Seto; Joks, Rauno; Nowakowski, Maja; Durkin, Helen G.

doi:10.4049/jimmunol.181.7.4761

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…DMSO (0.1%–1%) (MilliporeSigma, Burlington, MA) was used as the control. As in our earlier studies, levels of IgE in cultures supernatants peaked on day 10 11,12 . On day 10, cells were recovered, counted, viability determined and the levels/extent of phosphorylation of MAPK (P38, ERK and JNK) expressed by leucocyte subsets determined (flow cytometry).…”

Section: Methodsmentioning

confidence: 82%

“…Distributions of blood lymphocyte (CD4+, CD8+ and CD19+) and monocyte (CD14+) subpopulations were determined as previously described 11,12 . Flow cytometric analysis was performed according to manufacturer's recommendations.…”

Section: Methodsmentioning

confidence: 99%

“…As in our earlier studies, levels of IgE in cultures supernatants peaked on day 10. 11,12 On day 10, cells were recovered, counted, viability determined and the levels/ extent of phosphorylation of MAPK (P38, ERK and JNK) expressed by leucocyte subsets determined (flow cytometry). Culture supernatants were collected and frozen at −80°C, for future studies (IgE production).…”

Section: Cell Culturesmentioning

confidence: 99%

“…Distributions of blood lymphocyte (CD4+, CD8+ and CD19+) and monocyte (CD14+) subpopulations were determined as previously described. 11,12 Flow cytometric analysis was performed according to manufacturer's recommendations. 2.3.3 PBMC (1 × l0 6 in 1 mL) were transferred to 12 × 75 mm tubes, to which PMA (400 mM) (Sigma Aldrich, Catalogue Number P1585) was added, and the tubes were incubated for 15 min at 37°C, and the cells washed in staining buffer.…”

Section: Flow Cytometrymentioning

confidence: 99%

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Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

Silverberg,

Smith‐Norowitz,

Kohlhoff

et al. 2023

Scand J Immunol

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Mitogen‐activated protein kinases (MAPK) activate cascades that regulate cell proliferation, differentiation and death. Phosphorylated (phos‐)p38 MAPK is a cell‐signalling pathway associated with Th2 cytokine responses, which is required for immunoglobulin (Ig)E production. It is unknown whether MAPK are associated with IgE production. We examine the evidence linking p38 MAPK to inflammatory responses. Phos‐p38, extracellular signal‐related kinase (ERK) and c‐JUN‐n terminal (JNK) MAPK expression by blood leucocyte subsets and levels of serum Igs were measured in blood from adults with asthma and/or rhinoconjunctivitis (N = 28) and non‐asthma (N = 10) (flow cytometry, microfluorenzymeimmunoassay). Peripheral blood mononuclear cells (PBMC) from allergic subjects were cultured for 10 days ± anti‐CD40/recombinant IL‐4 ± inhibitor of phos‐P38. Culture supernatants were assayed for IgE (ELISA). Phos‐p38 MAPK expression by all leucocyte subsets of allergic subjects was associated with serum IgE levels (p ≤ 0.01), after adjusting for cell counts, age, sex, race and smoking status (p ≤ 0.04). Leucocyte expression of phos‐ERK and JNK did not correlate with IgE (p = 0.09–0.99). Instead, phos‐ERK expression was associated with serum IgG. When PBMC from atopic subjects were cultured for 10 days with anti‐CD40/rhIL‐4, IgE levels were 26.2 ± 18 ng/mL. Inclusion of SB202190 (5–20 μg/mL), a specific inhibitor of phos‐p38 MAPK, in culture suppressed IgE production in dose‐dependent manner, with peak suppression obtained with SB202190 at 20 μg/mL (82.1% ± 11.8) (p = 0.0001), with virtually no cytotoxicity (<5%). Different MAPK pathways may be associated with IgE (p38) and IgG (ERK) responses. Phos‐p38 MAPK can be a potential anti‐allergy drug target.

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Section: Methodsmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

Silverberg,

Smith‐Norowitz,

Kohlhoff

et al. 2023

Scand J Immunol

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“…Several studies have described changes of CD45RO/RA cells in patients with seasonal allergies [16–19], however, less is known about changes in central memory and effector memory cell subsets in these patients. In particular, studies describing the changes caused by pollen exposure in T cell subpopulations of patients suffering from allergic rhinitis are required.…”

Section: Introductionmentioning

confidence: 99%

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

Schramm

Jasiewicz-Honkisz

Osmenda

et al. 2016

Allergy Asthma Clin Immunol

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BackgroundAllergic rhinitis affects 10–30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma.MethodsSixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1–3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test.ResultsAs expected, an increase in the percentage of IL‐4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure.ConclusionsTh1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-016-0157-6) contains supplementary material, which is available to authorized users.

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Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs

Joks

Durkin

2011

Pharmacological Research

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Two Distinct T Cell Subsets, CD4+ and CD8+CD60+, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses

Cited by 4 publications

References 31 publications

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs

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