Phenotypic analysis of perennial airborne allergen‐specific CD4<sup>+</sup> T cells in atopic and non‐atopic individuals

Crack, L; Chan, Huan; McPherson, Tess; Ogg, Graham S.

doi:10.1111/j.1365-2222.2011.03819.x

Cited by 11 publications

(9 citation statements)

References 64 publications

(65 reference statements)

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“…Confirmation of a strong correlation between Th2 cells responding to cat dander and levels of cat-dander IgE in this paper provides further support, in addition to confirmation of phenotypic data established using MHC class II tetramers. In keeping with our previous studies of responses to birch allergen [3] and other studies [7,8,11], we found that responses to cat and grass allergens were very mixed, with activated Th2, Th1 and Tr1-like lymphocytes identified in varying proportions in allergic and non-allergic participants. Although the frequency of Th2 cells was significantly higher amongst allergic participants compared to non-allergic controls, there was considerable overlap, and the frequency of Th1 cells did not differ significantly.…”

Section: Discussionsupporting

confidence: 91%

“…In particular, T cells specific for seasonal allergens have been reported as CD27 low , late-differentiated cells [4-6], whereas perennial allergen-specific T cell responses are CD27 high , consistent with a central memory/early differentiated phenotype [7,8]. Our previous study did demonstrate a significantly higher frequency of CD27 - late-differentiated T cells responding to birch pollen in allergic individuals compared to non-atopic controls [3].…”

Section: Introductionmentioning

confidence: 94%

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Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

et al. 2013

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BackgroundAllergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens.ResultsWe identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens.ConclusionsThe findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 94%

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

et al. 2013

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“…The relationship between these T cell subsets was dysregulated in the birch allergic group, with abrogation of the IL-10 response and a weaker, non-significant correlation between Th2 and Th1 cell frequency at an increased Th2: Th1 ratio. However, the concentration of circulating birch IgE correlated closely with the frequency of IL-4 positive T cells rather than the Th2: Th1 ratio, consistent with the observations of Crack et al [11], suggesting that the absolute Th2 lymphocyte frequency represents an important parameter once sensitisation has occurred.…”

Section: Discussionsupporting

confidence: 89%

Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers

et al. 2013

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BackgroundAllergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We hypothesised that the relationship between these T cell subsets could be better defined using a short-term allergen stimulation system followed by direct analysis of CD154-positive T cells. Using peripheral blood samples from birch pollinosis patients and healthy non-atopic controls, we sought to explore the frequencies and phenotype of birch-stimulated CD154-positive T helper cells following ex vivo birch allergen stimulation.ResultsActivated CD154-positive Th1, Th2 and Tr1-like cells, that co-expressed IFNγ, IL-4 and IL-10 respectively, were identified in both birch-allergic and non-allergic participants. We observed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. The relationship between Th1, Th2 and Tr1-like responses was dysregulated in birch-allergic patients, with abrogation of the IL-10 response and a higher Th2: Th1 ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE within the birch-allergic group, and we confirmed previous reports of a more differentiated T cell phenotype in allergic subjects.ConclusionsThe findings demonstrate an important balance between IFNγ, IL-4 and IL-10 T cell responses to birch allergen in health, where Th2 responses to allergens were frequently observed, but apparently balanced by Th1 and regulatory responses. The detection of CD154 positive T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities.

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“…This is not unexpected because, regardless of atopic status, subjects may have allergen-specific T cells in their blood that can proliferate in vitro in response to allergen-derived peptides presented by APC [35–37]. Arguably, of more clinical importance is the resultant effector phenotype of allergen-stimulated T cells as this is what ultimately directs the type of immune response and generation of allergen-specific IgE antibody.…”

Section: Discussionmentioning

confidence: 99%

Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity

et al. 2017

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Crustacean allergy is a major cause of food-induced anaphylaxis. We showed previously that heating increases IgE reactivity of crustacean allergens. Here we investigate the effects of thermal processing of crustacean extracts on cellular immune reactivity. Raw and cooked black tiger prawn, banana prawn, mud crab and blue swimmer crab extracts were prepared and IgE reactivity assessed by ELISA. Mass spectrometry revealed a mix of several allergens in the raw mud crab extract but predominant heat-stable tropomyosin in the cooked extract. PBMC from crustacean-allergic and non-atopic control subjects were cultured with the crab and prawn extracts and proliferation of lymphocyte subsets was analysed by CFSE labelling and flow cytometry. Effector responses were assessed by intracellular IL-4 and IFN-γ, and regulatory T (CD4+CD25+CD127loFoxp3+) cell proportions in cultures were also compared by flow cytometry. For each crustacean species, the cooked extract had greater IgE reactivity than the raw (mud crab p<0.05, other species p<0.01). In contrast, there was a trend for lower PBMC proliferative responses to cooked compared with raw extracts. In crustacean-stimulated PBMC cultures, dividing CD4+ and CD56+ lymphocytes showed higher IL-4+/IFN-γ+ ratios for crustacean-allergic subjects than for non-atopics (p<0.01), but there was no significant difference between raw and cooked extracts. The percentage IL-4+ of dividing CD4+ cells correlated with total and allergen-specific IgE levels (prawns p<0.01, crabs p<0.05). Regulatory T cell proportions were lower in cultures stimulated with cooked compared with raw extracts (mud crab p<0.001, banana prawn p<0.05). In conclusion, cooking did not substantially alter overall T cell proliferative or cytokine reactivity of crustacean extracts, but decreased induction of Tregs. In contrast, IgE reactivity of cooked extracts was increased markedly. These novel findings have important implications for improved diagnostics, managing crustacean allergy and development of future therapeutics. Assessment of individual allergen T cell reactivity is required.

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Phenotypic analysis of perennial airborne allergen‐specific CD4⁺ T cells in atopic and non‐atopic individuals

Abstract: Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals.

Cited by 11 publications

References 64 publications

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers

Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity

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Phenotypic analysis of perennial airborne allergen‐specific CD4+ T cells in atopic and non‐atopic individuals

Abstract: Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals.

Cited by 11 publications

References 64 publications

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers

Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity

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Phenotypic analysis of perennial airborne allergen‐specific CD4⁺ T cells in atopic and non‐atopic individuals