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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 c) OPLS-DA loadings column plot depicting the associations between allergic disease at36 months, that is, children diagnosed with eczema, asthma, food allergy and/or allergicrhinoconjunctivitis, while specific IgE was not a criterion for a clinical diagnosis of allergy, andX-variables, including CD4+ T cells that are (a)FOXP3+CD25high or (c) FOXP3+CD25+,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ or α4β7+ atbirth, 3–5 days, and 1, 4, 18 and 36 months of age. Measurements of PHA-inducedcytokine production by mononuclear cells at 4, 18 and 36 months and OVA- and birch allergenextract-induced cytokine production at 36 months of age were also included in the analyses.X-variables with bars projected in the same direction as allergy are positively associated, whereasparameters in the opposite direction are inversely related to allergy at this age. The larger thebar and smaller the error bar, the stronger and more certain is the contribution to the model. TheOPLS-DA loadings column plots are based on X-variables with VIP-values ≥ 0.9. R2Yindicates how well the variation of Y is explained, while Q2 indicates how well Y can be predicted.R2Y: (a) = 0.33, (c) = 0.32. Q2:(a) = 0.18, (c) = 0.21. (b) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from children who were allergic or notat 36 months of age. (d) The proportions of FOXP3+CD25+cells within the CD4+ T cell population at 18 and 36 months of age inchildren who were allergic or not at 36 months of age. Each dot represents an individual, andhorizontal bars indicate median value. Statistical differences between the groups were calculatedusing two-tailed Mann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05).
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fig03: (a and c) OPLS-DA loadings column plot depicting the associations between allergic disease at36 months, that is, children diagnosed with eczema, asthma, food allergy and/or allergicrhinoconjunctivitis, while specific IgE was not a criterion for a clinical diagnosis of allergy, andX-variables, including CD4+ T cells that are (a)FOXP3+CD25high or (c) FOXP3+CD25+,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ or α4β7+ atbirth, 3–5 days, and 1, 4, 18 and 36 months of age. Measurements of PHA-inducedcytokine production by mononuclear cells at 4, 18 and 36 months and OVA- and birch allergenextract-induced cytokine production at 36 months of age were also included in the analyses.X-variables with bars projected in the same direction as allergy are positively associated, whereasparameters in the opposite direction are inversely related to allergy at this age. The larger thebar and smaller the error bar, the stronger and more certain is the contribution to the model. TheOPLS-DA loadings column plots are based on X-variables with VIP-values ≥ 0.9. R2Yindicates how well the variation of Y is explained, while Q2 indicates how well Y can be predicted.R2Y: (a) = 0.33, (c) = 0.32. Q2:(a) = 0.18, (c) = 0.21. (b) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from children who were allergic or notat 36 months of age. (d) The proportions of FOXP3+CD25+cells within the CD4+ T cell population at 18 and 36 months of age inchildren who were allergic or not at 36 months of age. Each dot represents an individual, andhorizontal bars indicate median value. Statistical differences between the groups were calculatedusing two-tailed Mann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05).

Mentions: Although allergy is linked to sensitization, children may be allergic but not sensitized, as wellas sensitized but not allergic (Table1). Hence, we examinedhow the T cell variables described above were related to allergic disease at 18 and 36 monthsof age. The OPLS-DA loadings column plot in Fig.3a is basedon parameters with VIP values ≥ 0.9. Being allergic at 36 months of age wasassociated with mononuclear cells with a higher capacity to produce the Th2-related cytokines IL-5and IL-13 at both 18 and 36 months of life. However, no T cell variables were inverselyrelated to allergic disease. Univariate analyses confirmed that allergic children producedsignificantly higher levels of IL-5 upon PHA stimulation at 36, but not at 18 months of age(Fig.3b). A clinical diagnosis of allergy at18 months of age did not display any specific association patterns with the T cell variables(data not shown). These results suggest that, in contrast to sensitization, a clinical diagnosis ofallergy is not associated with higher proportions of neonatalFOXP3+CD25high putative Tregs within the CD4+ T cellpopulation. Moreover, as one could expect, being allergic is related to a higher capacity to producethe Th2-related cytokine IL-5.


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 c) OPLS-DA loadings column plot depicting the associations between allergic disease at36 months, that is, children diagnosed with eczema, asthma, food allergy and/or allergicrhinoconjunctivitis, while specific IgE was not a criterion for a clinical diagnosis of allergy, andX-variables, including CD4+ T cells that are (a)FOXP3+CD25high or (c) FOXP3+CD25+,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ or α4β7+ atbirth, 3–5 days, and 1, 4, 18 and 36 months of age. Measurements of PHA-inducedcytokine production by mononuclear cells at 4, 18 and 36 months and OVA- and birch allergenextract-induced cytokine production at 36 months of age were also included in the analyses.X-variables with bars projected in the same direction as allergy are positively associated, whereasparameters in the opposite direction are inversely related to allergy at this age. The larger thebar and smaller the error bar, the stronger and more certain is the contribution to the model. TheOPLS-DA loadings column plots are based on X-variables with VIP-values ≥ 0.9. R2Yindicates how well the variation of Y is explained, while Q2 indicates how well Y can be predicted.R2Y: (a) = 0.33, (c) = 0.32. Q2:(a) = 0.18, (c) = 0.21. (b) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from children who were allergic or notat 36 months of age. (d) The proportions of FOXP3+CD25+cells within the CD4+ T cell population at 18 and 36 months of age inchildren who were allergic or not at 36 months of age. Each dot represents an individual, andhorizontal bars indicate median value. Statistical differences between the groups were calculatedusing two-tailed Mann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05).
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Related In: Results  -  Collection

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fig03: (a and c) OPLS-DA loadings column plot depicting the associations between allergic disease at36 months, that is, children diagnosed with eczema, asthma, food allergy and/or allergicrhinoconjunctivitis, while specific IgE was not a criterion for a clinical diagnosis of allergy, andX-variables, including CD4+ T cells that are (a)FOXP3+CD25high or (c) FOXP3+CD25+,CTLA-4+CD25+, CD45RO+,HLA-DR+, CCR4+ or α4β7+ atbirth, 3–5 days, and 1, 4, 18 and 36 months of age. Measurements of PHA-inducedcytokine production by mononuclear cells at 4, 18 and 36 months and OVA- and birch allergenextract-induced cytokine production at 36 months of age were also included in the analyses.X-variables with bars projected in the same direction as allergy are positively associated, whereasparameters in the opposite direction are inversely related to allergy at this age. The larger thebar and smaller the error bar, the stronger and more certain is the contribution to the model. TheOPLS-DA loadings column plots are based on X-variables with VIP-values ≥ 0.9. R2Yindicates how well the variation of Y is explained, while Q2 indicates how well Y can be predicted.R2Y: (a) = 0.33, (c) = 0.32. Q2:(a) = 0.18, (c) = 0.21. (b) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from children who were allergic or notat 36 months of age. (d) The proportions of FOXP3+CD25+cells within the CD4+ T cell population at 18 and 36 months of age inchildren who were allergic or not at 36 months of age. Each dot represents an individual, andhorizontal bars indicate median value. Statistical differences between the groups were calculatedusing two-tailed Mann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05).
Mentions: Although allergy is linked to sensitization, children may be allergic but not sensitized, as wellas sensitized but not allergic (Table1). Hence, we examinedhow the T cell variables described above were related to allergic disease at 18 and 36 monthsof age. The OPLS-DA loadings column plot in Fig.3a is basedon parameters with VIP values ≥ 0.9. Being allergic at 36 months of age wasassociated with mononuclear cells with a higher capacity to produce the Th2-related cytokines IL-5and IL-13 at both 18 and 36 months of life. However, no T cell variables were inverselyrelated to allergic disease. Univariate analyses confirmed that allergic children producedsignificantly higher levels of IL-5 upon PHA stimulation at 36, but not at 18 months of age(Fig.3b). A clinical diagnosis of allergy at18 months of age did not display any specific association patterns with the T cell variables(data not shown). These results suggest that, in contrast to sensitization, a clinical diagnosis ofallergy is not associated with higher proportions of neonatalFOXP3+CD25high putative Tregs within the CD4+ T cellpopulation. Moreover, as one could expect, being allergic is related to a higher capacity to producethe Th2-related cytokine IL-5.

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