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High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood.

Strömbeck A, Rabe H, Lundell AC, Andersson K, Johansen S, Adlerberth I, Wold AE, Hesselmar B, Rudin A - Clin. Exp. Allergy (2014)

Bottom Line: The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children.Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

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Related in: MedlinePlus

(a and b) OPLS discriminant analysis (OPLS-DA) score scatter plot displaying the separation ofsensitized, that is, specific IgE to food and/or inhalant allergens, (filled circles) andnon-sensitized (open circles) children at (a) 18 and (b) 36 months of age based onX-variables, including CD4+ T cells that areFOXP3+CD25high, CTLA-4+CD25+,CD45RO+, HLA-DR+, CCR4+ orα4β7+ at birth, 3–5 days, and at 1, 4, 18, 36, monthsof age. Measurements of PHA-induced cytokine production by mononuclear cells at 4, 18 and36 months and OVA- and birch allergen extract-induced cytokine production at 36 monthsof age were also included in the analyses. For sensitization at 18 months, immune parametersmeasured at 36 months were not included. R2Y indicates how well the variation of Y isexplained, while Q2 indicates how well Y can be predicted. (c and d) OPLS-DA loadings column plotsdepicting the associations between the X-variables described above and sensitization at (c) 18 and(d) 36 months of age. X-variables with bars projected in the same direction as sensitizationare positively associated, whereas bars in the opposite direction are inversely related tosensitization at the respective ages. The larger the bar and smaller the error bar, the stronger andmore certain is the contribution to the model. The OPLS loadings column plots are based onX-variables with VIP values (c) ≥ 0.8 and (d) ≥ 0.9. R2Y:(c) = 0.28, (d) = 0.37. Q2:(c) = 0.23, (d) = 0.24.
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fig01: (a and b) OPLS discriminant analysis (OPLS-DA) score scatter plot displaying the separation ofsensitized, that is, specific IgE to food and/or inhalant allergens, (filled circles) andnon-sensitized (open circles) children at (a) 18 and (b) 36 months of age based onX-variables, including CD4+ T cells that areFOXP3+CD25high, CTLA-4+CD25+,CD45RO+, HLA-DR+, CCR4+ orα4β7+ at birth, 3–5 days, and at 1, 4, 18, 36, monthsof age. Measurements of PHA-induced cytokine production by mononuclear cells at 4, 18 and36 months and OVA- and birch allergen extract-induced cytokine production at 36 monthsof age were also included in the analyses. For sensitization at 18 months, immune parametersmeasured at 36 months were not included. R2Y indicates how well the variation of Y isexplained, while Q2 indicates how well Y can be predicted. (c and d) OPLS-DA loadings column plotsdepicting the associations between the X-variables described above and sensitization at (c) 18 and(d) 36 months of age. X-variables with bars projected in the same direction as sensitizationare positively associated, whereas bars in the opposite direction are inversely related tosensitization at the respective ages. The larger the bar and smaller the error bar, the stronger andmore certain is the contribution to the model. The OPLS loadings column plots are based onX-variables with VIP values (c) ≥ 0.8 and (d) ≥ 0.9. R2Y:(c) = 0.28, (d) = 0.37. Q2:(c) = 0.23, (d) = 0.24.

Mentions: Using multivariate discriminant analysis by OPLS (orthogonal projections to latent structures),we investigated sensitization at 18 or 36 months of age in relation to proportions ofCD4+ T cell subsets (FOXP3+CD25high,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ and α4β7+) atbirth, 3–5 days of age and at 1, 4, 18 and 36 months of age, as well ascytokine production (IL-1β, TNF, IL-6, IFN-γ, IL-5 and IL-13) by peripheral bloodmononuclear cells after stimulation with PHA (at 4, 18 and 36 months of age), birch allergenextract or ovalbumin (at 36 months of age). For sensitization at 18 months of age,immune parameters measured at 36 months were not included in the analysis. The OPLS-DAscatter plots, in Figs1a and b, indicated that children whowere sensitized (filled circles) and non-sensitized (open circles) at 18 or 36 months of age,respectively, could be separated based on the T cell variables described above.


High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood.

Strömbeck A, Rabe H, Lundell AC, Andersson K, Johansen S, Adlerberth I, Wold AE, Hesselmar B, Rudin A - Clin. Exp. Allergy (2014)

(a and b) OPLS discriminant analysis (OPLS-DA) score scatter plot displaying the separation ofsensitized, that is, specific IgE to food and/or inhalant allergens, (filled circles) andnon-sensitized (open circles) children at (a) 18 and (b) 36 months of age based onX-variables, including CD4+ T cells that areFOXP3+CD25high, CTLA-4+CD25+,CD45RO+, HLA-DR+, CCR4+ orα4β7+ at birth, 3–5 days, and at 1, 4, 18, 36, monthsof age. Measurements of PHA-induced cytokine production by mononuclear cells at 4, 18 and36 months and OVA- and birch allergen extract-induced cytokine production at 36 monthsof age were also included in the analyses. For sensitization at 18 months, immune parametersmeasured at 36 months were not included. R2Y indicates how well the variation of Y isexplained, while Q2 indicates how well Y can be predicted. (c and d) OPLS-DA loadings column plotsdepicting the associations between the X-variables described above and sensitization at (c) 18 and(d) 36 months of age. X-variables with bars projected in the same direction as sensitizationare positively associated, whereas bars in the opposite direction are inversely related tosensitization at the respective ages. The larger the bar and smaller the error bar, the stronger andmore certain is the contribution to the model. The OPLS loadings column plots are based onX-variables with VIP values (c) ≥ 0.8 and (d) ≥ 0.9. R2Y:(c) = 0.28, (d) = 0.37. Q2:(c) = 0.23, (d) = 0.24.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4215110&req=5

fig01: (a and b) OPLS discriminant analysis (OPLS-DA) score scatter plot displaying the separation ofsensitized, that is, specific IgE to food and/or inhalant allergens, (filled circles) andnon-sensitized (open circles) children at (a) 18 and (b) 36 months of age based onX-variables, including CD4+ T cells that areFOXP3+CD25high, CTLA-4+CD25+,CD45RO+, HLA-DR+, CCR4+ orα4β7+ at birth, 3–5 days, and at 1, 4, 18, 36, monthsof age. Measurements of PHA-induced cytokine production by mononuclear cells at 4, 18 and36 months and OVA- and birch allergen extract-induced cytokine production at 36 monthsof age were also included in the analyses. For sensitization at 18 months, immune parametersmeasured at 36 months were not included. R2Y indicates how well the variation of Y isexplained, while Q2 indicates how well Y can be predicted. (c and d) OPLS-DA loadings column plotsdepicting the associations between the X-variables described above and sensitization at (c) 18 and(d) 36 months of age. X-variables with bars projected in the same direction as sensitizationare positively associated, whereas bars in the opposite direction are inversely related tosensitization at the respective ages. The larger the bar and smaller the error bar, the stronger andmore certain is the contribution to the model. The OPLS loadings column plots are based onX-variables with VIP values (c) ≥ 0.8 and (d) ≥ 0.9. R2Y:(c) = 0.28, (d) = 0.37. Q2:(c) = 0.23, (d) = 0.24.
Mentions: Using multivariate discriminant analysis by OPLS (orthogonal projections to latent structures),we investigated sensitization at 18 or 36 months of age in relation to proportions ofCD4+ T cell subsets (FOXP3+CD25high,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ and α4β7+) atbirth, 3–5 days of age and at 1, 4, 18 and 36 months of age, as well ascytokine production (IL-1β, TNF, IL-6, IFN-γ, IL-5 and IL-13) by peripheral bloodmononuclear cells after stimulation with PHA (at 4, 18 and 36 months of age), birch allergenextract or ovalbumin (at 36 months of age). For sensitization at 18 months of age,immune parameters measured at 36 months were not included in the analysis. The OPLS-DAscatter plots, in Figs1a and b, indicated that children whowere sensitized (filled circles) and non-sensitized (open circles) at 18 or 36 months of age,respectively, could be separated based on the T cell variables described above.

Bottom Line: The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children.Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Show MeSH
Related in: MedlinePlus