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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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(a and b) The proportion of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of age amongnon-farmers' children who were sensitized, that is, specific IgE to food and/or inhalantallergens, or non-sensitized at (a) 18 and (b) 36 months of age. (c) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from non-farmers' children whowere allergic, 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, ornot at 36 months of age. Each dot represents an individual, and horizontal bars indicatemedian values. Statistical differences between the groups were calculated using two-tailedMann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05 and **P ≤ 0.01).
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fig04: (a and b) The proportion of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of age amongnon-farmers' children who were sensitized, that is, specific IgE to food and/or inhalantallergens, or non-sensitized at (a) 18 and (b) 36 months of age. (c) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from non-farmers' children whowere allergic, 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, ornot at 36 months of age. Each dot represents an individual, and horizontal bars indicatemedian values. Statistical differences between the groups were calculated using two-tailedMann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05 and **P ≤ 0.01).

Mentions: Several independent studies have shown that the prevalence of allergy is significantly loweramong children raised in a farming environment 19,27. In the present cohort, we found a significantly lowerprevalence of allergic disease among children growing up on dairy farms (7% at18 months, 4% at 36 months) than among the children growing up on thecountryside in the same area, but not on farms (35% at 18 months,P = 0.02; 32% at 36 months,P = 0.02). However, there was no differenceregarding the prevalence of sensitization between these two groups (11% vs. 17% at18 months, P = 0.7; 27% vs.26% at 36 months, P = 1.0).Thus, farming environment was not likely to be a confounding factor for the positive associationsobserved between high proportions of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of life and subsequentsensitization. Hence, after exclusion of farmers' children from the univariate analyses shownin Figs2a and b, the same patterns were observed regardinghigher proportions of FOXP3+CD25high T cells at birth as well as at3 days of life and sensitization later in childhood (Fig.4a and b). Indeed, children who were sensitized at 18 months of age had significantlyhigher proportions of FOXP3+CD25high T cells at birth and at3 days of life than children who did not become sensitized (Fig.4a). Although not statistically significant, this pattern was also observed forchildren sensitized at 36 months of age (Fig.4b).Further, exclusion of farmers' children from the analysis did not alter the outcome thatchildren with allergic disease at 36 months of age produced significantly higher levels ofPHA-induced IL-5 at 36 months of age than non-allergic children (Fig.4c). Taken together, these results indicate that farming environment perse is not likely to be a confounding factor for the associations observed between highproportions of FOXP3+CD25high T cells at birth and at 3 days oflife and sensitization later in childhood.


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) The proportion of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of age amongnon-farmers' children who were sensitized, that is, specific IgE to food and/or inhalantallergens, or non-sensitized at (a) 18 and (b) 36 months of age. (c) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from non-farmers' children whowere allergic, 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, ornot at 36 months of age. Each dot represents an individual, and horizontal bars indicatemedian values. Statistical differences between the groups were calculated using two-tailedMann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05 and **P ≤ 0.01).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4215110&req=5

fig04: (a and b) The proportion of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of age amongnon-farmers' children who were sensitized, that is, specific IgE to food and/or inhalantallergens, or non-sensitized at (a) 18 and (b) 36 months of age. (c) The concentration ofPHA-induced production of IL-5 (pg/mL) by mononuclear cells from non-farmers' children whowere allergic, 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, ornot at 36 months of age. Each dot represents an individual, and horizontal bars indicatemedian values. Statistical differences between the groups were calculated using two-tailedMann–Whitney U-test.P ≤ 0.05 was regarded as significant(*P ≤ 0.05 and **P ≤ 0.01).
Mentions: Several independent studies have shown that the prevalence of allergy is significantly loweramong children raised in a farming environment 19,27. In the present cohort, we found a significantly lowerprevalence of allergic disease among children growing up on dairy farms (7% at18 months, 4% at 36 months) than among the children growing up on thecountryside in the same area, but not on farms (35% at 18 months,P = 0.02; 32% at 36 months,P = 0.02). However, there was no differenceregarding the prevalence of sensitization between these two groups (11% vs. 17% at18 months, P = 0.7; 27% vs.26% at 36 months, P = 1.0).Thus, farming environment was not likely to be a confounding factor for the positive associationsobserved between high proportions of FOXP3+CD25high cells within theCD4+ T cell population at birth and at 3 days of life and subsequentsensitization. Hence, after exclusion of farmers' children from the univariate analyses shownin Figs2a and b, the same patterns were observed regardinghigher proportions of FOXP3+CD25high T cells at birth as well as at3 days of life and sensitization later in childhood (Fig.4a and b). Indeed, children who were sensitized at 18 months of age had significantlyhigher proportions of FOXP3+CD25high T cells at birth and at3 days of life than children who did not become sensitized (Fig.4a). Although not statistically significant, this pattern was also observed forchildren sensitized at 36 months of age (Fig.4b).Further, exclusion of farmers' children from the analysis did not alter the outcome thatchildren with allergic disease at 36 months of age produced significantly higher levels ofPHA-induced IL-5 at 36 months of age than non-allergic children (Fig.4c). Taken together, these results indicate that farming environment perse is not likely to be a confounding factor for the associations observed between highproportions of FOXP3+CD25high T cells at birth and at 3 days oflife and sensitization later in childhood.

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