Dynamics of antigen-specific helper T cells at the initiation of airway eosinophilic inflammation

Kaminuma, Osamu; Fujimura, H.; Fushimi, Keiko; Nakata, Aya; Sakai, Atsuko; Chishima, Susumu; Ogawa, Koji; Kikuchi, Motohiro; Kikkawa, Hideo; Akiyama, Kazuo; Mori, Akio

doi:10.1002/1521-4141(200109)31:9<2669::aid-immu2669>3.0.co;2-y

Cited by 25 publications

(26 citation statements)

References 46 publications

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“…We detected infiltrated CD4 T cells at the near surface area of the asthmatic lung. Migration of CD4 T cells into the parenchyma or through the endothelial cells of the lung vessels has been reported (33). The imaging system used here is useful for the quantitative detection of the migrated lymphocytes into the asthmatic lung, since the number of lymphocytes including Th2 cells is relatively small among inflammatory cells such as eosinophils.…”

Section: Discussionmentioning

confidence: 89%

“…It is known that the expression of VCAM-1 on endothelial cells is induced in the inflamed lung and that VCAM-1 expression is critical for the recruitment of allergen-specific T cells and eosinophils during allergic airway inflammation (32,33). VCAM-1/ VLA-4 interaction was shown to be important for the recruitment of T cells in the inflamed tissues (32).…”

Section: Discussionmentioning

confidence: 99%

“…VCAM-1 expression is induced in the asthmatic lung, and the VCAM-1/VLA-4 interaction is critical for the migration of T cells and the induction of Th2-dependent airway inflammation (32,33). To test the involvement of VCAM-1 in the CD69-dependent airway inflammation, an immunofluorescent staining analysis with anti-VCAM-1 was performed.…”

Section: Reduced Vcam-1 Induction and Th2 Cell Migration In The Asthmmentioning

confidence: 99%

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CD69 Controls the Pathogenesis of Allergic Airway Inflammation

Miki-Hosokawa

Hasegawa

Iwamura

et al. 2009

The Journal of Immunology

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Airway inflammation and airway hyperresponsiveness are central issues in the pathogenesis of asthma. CD69 is a membrane molecule transiently expressed on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. In CD69-deficient mice, OVA-induced eosinophilic airway inflammation, mucus hyperproduction, and airway hyperresponsiveness were attenuated. Cell transfer of Ag-primed wild-type but not CD69-deficient CD4 T cells restored the induction of allergic inflammation in CD69-deficient mice, indicating a critical role of CD69 expressed on CD4 T cells. Th2 responses induced by CD69-deficient CD4 T cells in the lung were attenuated, and the migration of CD4 T cells into the asthmatic lung was severely compromised. The expression of VCAM-1 was also substantially altered, suggesting the involvement of VCAM-1 in the CD69-dependent migration of Th2 cells into the asthmatic lung. Interestingly, the administration of anti-CD69 Ab inhibited the induction of the OVA-induced airway inflammation and hyperresponsiveness. This inhibitory effect induced by the CD69 mAb was observed even after the airway challenge with OVA. These results indicate that CD69 plays a crucial role in the pathogenesis of allergen-induced eosinophilic airway inflammation and hyperresponsiveness and that CD69 could be a possible therapeutic target for asthmatic patients.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Reduced Vcam-1 Induction and Th2 Cell Migration In The Asthmmentioning

confidence: 99%

See 1 more Smart Citation

CD69 Controls the Pathogenesis of Allergic Airway Inflammation

Miki-Hosokawa

Hasegawa

Iwamura

et al. 2009

The Journal of Immunology

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“…In the murine asthma model, IL-12 contributed to the recruitment of eosinophils into the respiratory tract via the induction of VCAM-1 on local vascular epithelial cells. 35 Thus, the deletion of the IL-12 gene (p40) resulted in a substantial reduction in the airway recruitment of eosinophils and in the expression of VCAM-1 when compared with wild-type mice exhibiting an asthma-like reaction induced by systemic sensitization followed by nasal OVA. 36 In addition, selective overexpression of IL-12p40 was noted in airway epithelial cells and bronchoalveolar lavage fluids of patients with asthma.…”

Section: Discussionmentioning

confidence: 99%

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Hino

Kweon

Fujihashi

et al. 2004

The American Journal of Pathology

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IL-12 consists of two disulfide-linked subunits, p40 and p35, that form functionally active heterodimers for the induction of Th1 cells. In contrast to IL-12 heterodimers, p40 monomers and homodimers possess inhibitory effects on Th1 cells leading to the creation of a Th2 environment. Although it has been shown that IL-12p40 acts as antagonist of IL-12p70 in vitro, no evidence is currently available whether IL-12p40 is functional in vivo. We now report that IL12p40 plays an important pathological role in an intestinal allergic disease. A high expression of IL12p40 protein was demonstrated in epithelial cells, dendritic cells, and macrophages in large but not small intestine of allergic diarrhea-induced mice. Interestingly, neutralization with anti-IL-12p40 mAbs reduced the incidence and delayed the onset of disease development. Lower levels of ovalbumin (OVA)-specific IgE Abs in serum were detected in anti-IL12p40 mAb-treated mice than in control Ab-treated mice. The secretion of Th2 cytokines and eotaxin by the mononuclear cells isolated from the large intestine of anti-IL-12p40 mAb-treated mice was significantly decreased. Finally, the removal of the IL-12p40 gene resulted in complete inhibition of disease development. These results show that over-expression of IL-12p40 is an important contributing factor for the generation of the dominant Th2-type environment in the large intestine of mice with allergic diarrhea.

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“…5). CD4 ϩ T cells from animals initially exposed to 2 and 4 wk of OVA expressed not only similar levels of the early activation marker CD69 (34,35) and the IL-2R CD25 (36,37), but also similar levels of T1/ST2, a marker of Th2 differentiation and a necessary factor in the development of eosinophilic airway inflammation (38 -40). The level of expression of these molecules was substantially higher than previously documented in naive animals.…”

Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

Świrski

Sajic

Robbins

et al. 2002

The Journal of Immunology

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In this study we investigated the impact of chronic allergen exposure on airway inflammation and humoral responses in sensitized mice. We observed marked eosinophilia in the bronchoalveolar lavage, lung tissue, and peripheral blood after 2 wk of exposure. In contrast, eosinophilia was markedly reduced by 3 wk and completely resolved by 4 wk of exposure, despite the continued presence of Ag. Decreases in airway eosinophilia were associated with a robust humoral response. We observed that levels of OVA-specific IgE, IgG1, and IgG2a increased during the course of exposure. To assess whether continuous exposure to Ag impacts the ability of the lung to respond to subsequent Ag challenge, mice were exposed to either 2 or 4 wk of OVA in the context of GM-CSF. All groups were then rested for 28 days and exposed to OVA on three consecutive days. We observed a significant decrease in airway eosinophilia and IL-5 expression in the bronchoalveolar lavage and serum in mice initially exposed to 4 wk of OVA, compared with animals exposed to 2 wk only. However, in both groups expression of B7.2 on dendritic cells as well as CD25, CD69, and T1/ST2 on CD4+ T cells was enhanced, suggesting immune activation. Delivery of rGM-CSF fully restored airway eosinophilia. This study shows that exposure to innocuous Ag alone does not lead to persistent eosinophilic airway inflammation, but rather to abrogated eosinophilia. This suppression can be reversed by GM-CSF.

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Dynamics of antigen-specific helper T cells at the initiation of airway eosinophilic inflammation

Cited by 25 publications

References 46 publications

CD69 Controls the Pathogenesis of Allergic Airway Inflammation

CD69 Controls the Pathogenesis of Allergic Airway Inflammation

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

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