CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation

Oh, Jae‐Won; Seroogy, Christine M.; Meyer, Everett; Akbari, Omid; Berry, Gerald J.; Fathman, C. Garrison; DeKruyff, Rosemarie H.; Umetsu, Dale T.

doi:10.1067/mai.2002.127512

Cited by 197 publications

(129 citation statements)

References 48 publications

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“…Similarly, the role of IL-10 in the development of allergic asthma has been controversial, with knockout studies suggesting that IL-10 can either enhance or suppress its development (53,54). However, more recent studies have proposed a prominent role for IL-10 in suppressing the development of allergic asthma, although the source may be T regulatory cells (55,56). One possibility is that the ratio of this cytokine in relation to the others being produced may be a critical factor in regulating the symptoms seen in this disease.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Mueller

August

2003

The Journal of Immunology

145

137

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Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, TH2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This TH2-type response suggests a prominent role for TH2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of TH2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK−/− mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the TH2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.

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Section: Discussionmentioning

confidence: 99%

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Mueller

August

2003

The Journal of Immunology

145

137

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“…21 The phenomenon of IL-10-producing T cells ameliorating atopic disorders was already found in several other models of tolerance induction, such as immunotherapy. 22,23 Moreover, it has been shown in both mice and human subjects that parasite-induced levels of IL-10 are protective toward the development of atopy. 24,25 These data indicate an important role for IL-10-producing T cells in the process of tolerance.…”

Section: Discussionmentioning

confidence: 99%

Cow's milk?specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

Tiemessen

2004

Journal of Allergy and Clinical Immunology

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Background: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. Objective: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. Methods: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. Results: Cow's milk-specific TCCs of children with persistent CMA were T H 2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-g and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. Conclusion: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milktolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-g. These findings suggest that activated CD4 + T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of

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“…In addition, BezerraSantos (2004) demonstrated spleen cells from orally treated-AFL mice produced higher levels of both IFN-γ and IL-10, when compared to control animals. The IL-10 production in acute infl ammatory diseases represents a favorable prognosis due to its anti-infl ammatory effect (Jae-Won et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cissampelos sympodialis Eichl. (Menispermaceae) inhibits anaphylactic shock reaction in murine allergic model

Bezerra-Santos¹,

Pecanha²,

Piuvezam³

2005

Rev. bras. farmacogn.

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The murine model of OVA-induced immediate allergic reaction was used to evaluate the effectiveness of intraperitoneal sub-acute treatment with the leaf hydroalcoholic extract of Cissampelos sympodialis (AFL) in the anaphylactic shock reaction, IgE production and the background proliferative response. BALB/c mice treated with AFL ranging from 200 to 400 mg/kg/day for 5 days before and during OVA-sensitization strongly reduced the animal death and promoted reduction in total and OVA-specifi c serum IgE level. Spleen cells from AFL-treated sensitized animals showed a decreased proliferative background response when compared with non-sensitized animals. These results demonstrated that sub-acute intraperitoneal treatment with Cissampelos sympodialis extract has an anti-allergic effect.

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CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation

Cited by 197 publications

References 48 publications

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Cow's milk?specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

Cissampelos sympodialis Eichl. (Menispermaceae) inhibits anaphylactic shock reaction in murine allergic model

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