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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.

Smith KA, Gray NJ, Saleh F, Cheek E, Frew AJ, Kern F, Tarzi MD - BMC Immunol. (2013)

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Brighton and Sussex Medical School, division of clinical medicine, pathogen-host-interactions group, University of Sussex, Brighton BN1 9PS, UK. M.Tarzi@bsms.ac.uk.

ABSTRACT

Background: Allergic 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.

Results: We 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.

Conclusions: The 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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Allergen-induced Th1, Th2 and Tr1-like cell populations in allergic and non-allergic participants. Data represents (a) CD154+IL-4+ Th2 cells, (b) CD154+IFNγ+ Th1 cells and (c) CD154+IL-10+ Tr1-like cells illustrated as the background-corrected frequency of positive cells per 106 CD4 T cells on a log scale, (d) Th2: Th1 ratio.
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Figure 3: Allergen-induced Th1, Th2 and Tr1-like cell populations in allergic and non-allergic participants. Data represents (a) CD154+IL-4+ Th2 cells, (b) CD154+IFNγ+ Th1 cells and (c) CD154+IL-10+ Tr1-like cells illustrated as the background-corrected frequency of positive cells per 106 CD4 T cells on a log scale, (d) Th2: Th1 ratio.

Mentions: Th1, Th2 and Tr1-like cells were defined as CD154+IFNγ+, CD154+IL-4+ and CD154+IL-10+, respectively (Figure 2). With respect to both cat and grass allergens, we observed very mixed and variable T cell responses in both allergic and non-allergic subjects. In the case of grass allergen, Th2 responses were convincingly greater than the non-allergic group (p = 0.01), but the parameter separated the cat-allergic and cat-tolerant group less completely (p = 0.03) (Figure 3a). There were no differences in the frequency of Th1 or Tr1-like responses between allergic and non-allergic participants in response to either cat or grass allergens (Figure 3b, c).


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.

Smith KA, Gray NJ, Saleh F, Cheek E, Frew AJ, Kern F, Tarzi MD - BMC Immunol. (2013)

Allergen-induced Th1, Th2 and Tr1-like cell populations in allergic and non-allergic participants. Data represents (a) CD154+IL-4+ Th2 cells, (b) CD154+IFNγ+ Th1 cells and (c) CD154+IL-10+ Tr1-like cells illustrated as the background-corrected frequency of positive cells per 106 CD4 T cells on a log scale, (d) Th2: Th1 ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228241&req=5

Figure 3: Allergen-induced Th1, Th2 and Tr1-like cell populations in allergic and non-allergic participants. Data represents (a) CD154+IL-4+ Th2 cells, (b) CD154+IFNγ+ Th1 cells and (c) CD154+IL-10+ Tr1-like cells illustrated as the background-corrected frequency of positive cells per 106 CD4 T cells on a log scale, (d) Th2: Th1 ratio.
Mentions: Th1, Th2 and Tr1-like cells were defined as CD154+IFNγ+, CD154+IL-4+ and CD154+IL-10+, respectively (Figure 2). With respect to both cat and grass allergens, we observed very mixed and variable T cell responses in both allergic and non-allergic subjects. In the case of grass allergen, Th2 responses were convincingly greater than the non-allergic group (p = 0.01), but the parameter separated the cat-allergic and cat-tolerant group less completely (p = 0.03) (Figure 3a). There were no differences in the frequency of Th1 or Tr1-like responses between allergic and non-allergic participants in response to either cat or grass allergens (Figure 3b, c).

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Brighton and Sussex Medical School, division of clinical medicine, pathogen-host-interactions group, University of Sussex, Brighton BN1 9PS, UK. M.Tarzi@bsms.ac.uk.

ABSTRACT

Background: Allergic 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.

Results: We 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.

Conclusions: The 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.

Show MeSH