Bystander T Cells Participate in Specific Response to Cockroach Antigen (CR) In Vitro

Walters, Curla S.; Tackey, Robert; Reece, Elena R.; Paluvoi, S

doi:10.1081/imm-120019212

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…However, in our study, no associations were observed between levels of cockroach and allergen-specific IgE antibody levels or allergen-specific T cell reactivity and disease phenotype/severity. CR-specific T cell responses have been characterized in relatively low detail ( 5 – 7 , 47 ), and very little information is available particularly addressing if T cells play a role in cockroach allergic sensitization. Although it has been shown that higher T cell reactivity is associated with allergen sensitization and asthma ( 48 ), future studies are warranted to elucidate to which extent T cell responses correlate with clinical symptoms or disease severity.…”

Section: Discussionmentioning

confidence: 99%

IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease

et al. 2021

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IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort. Ex vivo T cell activation (Ox40/PDL-1 expression) of PBMCs stimulated with peptide pools derived from 11 German cockroach proteins, including nine official cockroach allergens, plus chitinase and vitellogenin, was determined by flow cytometry. IgE prevalences to chitinase (17%) and hemocyanin (44%) were comparable to values for the other eight allergens that we previously reported (21–57%). Hemocyanin (Bla g 3), was a major allergen (one to which more than 50% of patients with an allergy to its source react) for a sub-group of 15 highly cockroach-sensitized subjects (IgE > 3.5 kUA/L: 53%). Chitinase was officially named as new allergen Bla g 12. Cockroach-specific IgE levels in plasma showed excellent correlation with the sum of 10 allergen-specific IgE (r = 0.94, p < 0.001). T cell reactivity to 11 proteins was highly variable among subjects, the highest being for vitellogenin, followed by Bla g 3. The main finding was that cockroach allergen-specific IgE and T cell reactivity patterns were unique per subject, and lacked immunodominant allergens and correlation with clinical phenotype/disease severity in the studied cohort. Knowing the subject-specific B/T cell reactivity profiles to a comprehensive panel of cockroach allergens will contribute to diagnosis of cockroach allergy and will be important for planning and assessing allergen immunotherapy outcomes, according to the allergen content in therapeutic cockroach extracts.

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Section: Discussionmentioning

confidence: 99%

IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease

et al. 2021

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“…Therefore, chronic Ag-specific Th2 inflammation can potentiate further naive T cell sensitization to distinct allergens in a process we have called collateral priming (Table I). We have used the term collateral priming to describe the process of activation of naive T cells to their cognate Ag by adaptive immune signals to contrast it with the phenomena known as bystander activation (32)(33)(34)(35). Although both processes involve activation of T cells by factors produced by a proximal but distinct T cell population, collateral priming is the activation of a naive T cell to its cognate Ag (as compared with an Ag-nonspecific response).…”

Section: Discussionmentioning

confidence: 99%

IL-4-Dependent Th2 Collateral Priming to Inhaled Antigens Independent of Toll-Like Receptor 4 and Myeloid Differentiation Factor 88

Eisenbarth¹,

Zhadkevich²,

Ranney³

et al. 2004

The Journal of Immunology

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Allergic asthma is an inflammatory lung disease thought to be initiated and directed by type 2 helper T cells responding to environmental Ags. The mechanisms by which allergens induce Th2-adaptive immune responses are not well understood, although it is now clear that innate immune signals are required to promote DC activation and Th2 sensitization to inhaled proteins. However, the effect of ongoing Th2 inflammation, as seen in chronic asthma, on naive lymphocyte activation has not been explored. It has been noted that patients with atopic disorders demonstrate an increased risk of developing sensitivities to new allergens. This suggests that signals from an adaptive immune response may facilitate sensitization to new Ags. We used a Th2-adoptive transfer murine model of asthma to identify a novel mechanism, termed “collateral priming,” in which naive CD4+ T cells are activated by adaptive rather than innate immune signals. Th2 priming to newly encountered Ags was dependent on the production of IL-4 by the transferred Th2 population but was independent of Toll-like receptor 4 signaling and the myeloid differentiation factor 88 Toll-like receptor signaling pathway. These results identify a novel mechanism of T cell priming in which an Ag-specific adaptive immune response initiates distinct Ag-specific T cell responses in the absence of classical innate immune system triggering signals.

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“…Several studies defined CR allergens based on IgE reactivity from sensitized individuals and correlated sensitization prevalence with severity of clinical symptoms 3,[9][10][11][12] . T cells, and in particular type 2 T helper cells, significantly contribute to the development of allergy and asthma [13][14][15] ; however, CR-specific T cell responses have been characterized in less detail [16][17][18][19][20][21] , and very little information is available particularly for the population most impacted by CR allergies, namely urban and under-resourced children.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of cockroach allergen-specific T cell responses in allergic sensitized children

Antunes,

Sutherland,

Frazier

et al. 2024

Preprint

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BACKGROUND: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. RESULTS: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFN production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. CONCLUSIONS: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

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Bystander T Cells Participate in Specific Response to Cockroach Antigen (CR) In Vitro

Cited by 5 publications

References 29 publications

IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease

IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease

IL-4-Dependent Th2 Collateral Priming to Inhaled Antigens Independent of Toll-Like Receptor 4 and Myeloid Differentiation Factor 88

Heterogeneity of cockroach allergen-specific T cell responses in allergic sensitized children

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