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Exposure to High Doses of Lipopolysaccharide during Ovalbumin Sensitization Prevents the Development of Allergic Th2 Responses to a Dietary Antigen.

Torii I, Shimizu S, Daimon T, Shinohara Y, Kudo T, Sato A, Tsujimura T - J Toxicol Pathol (2014)

Bottom Line: Mice sensitized with crude OVA developed Th2 responses including acute diarrhea, increases in serum OVA-specific IgE, dominant production of serum OVA-specific IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal and colonic tissues.On the other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells of tolerant mice.These results indicate that tolerance is induced in allergic mice by simultaneous exposure to LPS during sensitization with OVA and that a population of T cells producing IL-10 plays an important role in the tolerance induction.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

ABSTRACT
Food allergies are driven by aberrant T helper (Th) 2 cells. Lipopolysaccharide (LPS) influences the development of Th2-mediated diseases, but its role in food allergy and tolerance remains unclear. To address this issue, we established mouse models presenting allergic or tolerant responses to ovalbumin (OVA). Mice sensitized with crude OVA developed Th2 responses including acute diarrhea, increases in serum OVA-specific IgE, dominant production of serum OVA-specific IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal and colonic tissues. Sensitization of mice with crude OVA and LPS abrogated Th2-type responses observed in allergic mice. The level of OVA-specific proliferation in mesenteric lymph node CD4(+) T cells was comparable in allergic and tolerant mice, indicating that the tolerance is not caused by anergy and apoptosis of antigen-primed T cells. Expression of Th1- and Th2-type cytokines was suppressed in whole spleen cells and/or purified spleen CD4(+) T cells of tolerant mice, indicating that the tolerance was not caused by the shift from Th2 to Th1. On the other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells of tolerant mice. Furthermore, spleen CD4(+) T cells from tolerant mice suppressed the growth of CD4(+) T cells from DO11.10 mice in co-culture. These results indicate that tolerance is induced in allergic mice by simultaneous exposure to LPS during sensitization with OVA and that a population of T cells producing IL-10 plays an important role in the tolerance induction.

No MeSH data available.


Related in: MedlinePlus

Establishment of anallergic model. (A) The experimental protocol for induction of allergy in mice.BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100μg) at a 2-week interval (black arrows) and then challenged by intragastricadministration (ig) of cOVA (100 mg) on the indicated days (white arrows). Mice weresacrificed within 1 h after the last challenge (dotted arrow). Mice sensitized withPBS were used as a control. (B) Incidence of diarrhea. cOVA-sensitized (closedcircle) (n=8) and PBS control BALB/c ByJ mice (open circle) (n=3) were monitored for1 h, and diarrhea occurrence was assessed for 15 - 60 min after each challenge withcOVA. Similar results were obtained in 5 experiments carried out in this study, andthe representative results are shown. (C) Allergic reactions of the alimentarytract. (a) Mice sensitized with cOVA showed severe mucous diarrhea within 30 minafter challenge with cOVA. (b) The ceca and colons removed from cOVA-sensitized,cOVA-challenged mice showed severe edematous and hyperemic changes and containedwatery soft feces after repeated oral challenges with cOVA, and (c) those fromcontrol mice showed no edematous and hyperemic changes and contained solidfeces.
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fig_001: Establishment of anallergic model. (A) The experimental protocol for induction of allergy in mice.BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100μg) at a 2-week interval (black arrows) and then challenged by intragastricadministration (ig) of cOVA (100 mg) on the indicated days (white arrows). Mice weresacrificed within 1 h after the last challenge (dotted arrow). Mice sensitized withPBS were used as a control. (B) Incidence of diarrhea. cOVA-sensitized (closedcircle) (n=8) and PBS control BALB/c ByJ mice (open circle) (n=3) were monitored for1 h, and diarrhea occurrence was assessed for 15 - 60 min after each challenge withcOVA. Similar results were obtained in 5 experiments carried out in this study, andthe representative results are shown. (C) Allergic reactions of the alimentarytract. (a) Mice sensitized with cOVA showed severe mucous diarrhea within 30 minafter challenge with cOVA. (b) The ceca and colons removed from cOVA-sensitized,cOVA-challenged mice showed severe edematous and hyperemic changes and containedwatery soft feces after repeated oral challenges with cOVA, and (c) those fromcontrol mice showed no edematous and hyperemic changes and contained solidfeces.

Mentions: BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100 μg)prior to repeated intragastric challenges with a high dose of cOVA (100 mg) (Fig. 1AFig. 1.


Exposure to High Doses of Lipopolysaccharide during Ovalbumin Sensitization Prevents the Development of Allergic Th2 Responses to a Dietary Antigen.

Torii I, Shimizu S, Daimon T, Shinohara Y, Kudo T, Sato A, Tsujimura T - J Toxicol Pathol (2014)

Establishment of anallergic model. (A) The experimental protocol for induction of allergy in mice.BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100μg) at a 2-week interval (black arrows) and then challenged by intragastricadministration (ig) of cOVA (100 mg) on the indicated days (white arrows). Mice weresacrificed within 1 h after the last challenge (dotted arrow). Mice sensitized withPBS were used as a control. (B) Incidence of diarrhea. cOVA-sensitized (closedcircle) (n=8) and PBS control BALB/c ByJ mice (open circle) (n=3) were monitored for1 h, and diarrhea occurrence was assessed for 15 - 60 min after each challenge withcOVA. Similar results were obtained in 5 experiments carried out in this study, andthe representative results are shown. (C) Allergic reactions of the alimentarytract. (a) Mice sensitized with cOVA showed severe mucous diarrhea within 30 minafter challenge with cOVA. (b) The ceca and colons removed from cOVA-sensitized,cOVA-challenged mice showed severe edematous and hyperemic changes and containedwatery soft feces after repeated oral challenges with cOVA, and (c) those fromcontrol mice showed no edematous and hyperemic changes and contained solidfeces.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4217231&req=5

fig_001: Establishment of anallergic model. (A) The experimental protocol for induction of allergy in mice.BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100μg) at a 2-week interval (black arrows) and then challenged by intragastricadministration (ig) of cOVA (100 mg) on the indicated days (white arrows). Mice weresacrificed within 1 h after the last challenge (dotted arrow). Mice sensitized withPBS were used as a control. (B) Incidence of diarrhea. cOVA-sensitized (closedcircle) (n=8) and PBS control BALB/c ByJ mice (open circle) (n=3) were monitored for1 h, and diarrhea occurrence was assessed for 15 - 60 min after each challenge withcOVA. Similar results were obtained in 5 experiments carried out in this study, andthe representative results are shown. (C) Allergic reactions of the alimentarytract. (a) Mice sensitized with cOVA showed severe mucous diarrhea within 30 minafter challenge with cOVA. (b) The ceca and colons removed from cOVA-sensitized,cOVA-challenged mice showed severe edematous and hyperemic changes and containedwatery soft feces after repeated oral challenges with cOVA, and (c) those fromcontrol mice showed no edematous and hyperemic changes and contained solidfeces.
Mentions: BALB/c ByJ or BALB/c Cr mice were sensitized twice by i.p. injection of cOVA (100 μg)prior to repeated intragastric challenges with a high dose of cOVA (100 mg) (Fig. 1AFig. 1.

Bottom Line: Mice sensitized with crude OVA developed Th2 responses including acute diarrhea, increases in serum OVA-specific IgE, dominant production of serum OVA-specific IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal and colonic tissues.On the other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells of tolerant mice.These results indicate that tolerance is induced in allergic mice by simultaneous exposure to LPS during sensitization with OVA and that a population of T cells producing IL-10 plays an important role in the tolerance induction.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

ABSTRACT
Food allergies are driven by aberrant T helper (Th) 2 cells. Lipopolysaccharide (LPS) influences the development of Th2-mediated diseases, but its role in food allergy and tolerance remains unclear. To address this issue, we established mouse models presenting allergic or tolerant responses to ovalbumin (OVA). Mice sensitized with crude OVA developed Th2 responses including acute diarrhea, increases in serum OVA-specific IgE, dominant production of serum OVA-specific IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal and colonic tissues. Sensitization of mice with crude OVA and LPS abrogated Th2-type responses observed in allergic mice. The level of OVA-specific proliferation in mesenteric lymph node CD4(+) T cells was comparable in allergic and tolerant mice, indicating that the tolerance is not caused by anergy and apoptosis of antigen-primed T cells. Expression of Th1- and Th2-type cytokines was suppressed in whole spleen cells and/or purified spleen CD4(+) T cells of tolerant mice, indicating that the tolerance was not caused by the shift from Th2 to Th1. On the other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells of tolerant mice. Furthermore, spleen CD4(+) T cells from tolerant mice suppressed the growth of CD4(+) T cells from DO11.10 mice in co-culture. These results indicate that tolerance is induced in allergic mice by simultaneous exposure to LPS during sensitization with OVA and that a population of T cells producing IL-10 plays an important role in the tolerance induction.

No MeSH data available.


Related in: MedlinePlus