Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13

Miyahara, Nobuaki; Takeda, Katsuyuki; Kodama, Taku; Joetham, Anthony; Taube, Christian; Park, Jung Won; Miyahara, Satoko; Balhorn, Annette; Dakhama, Azzeddine; Gelfand, Erwin W.

doi:10.4049/jimmunol.172.4.2549

Cited by 102 publications

(102 citation statements)

References 61 publications

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“…Our data are in line with recent studies reporting on the effector role of CD8 ϩ T cells in allergic asthma (30,31) and strongly support the idea that the CD4 ϩ Th2 dogma in allergic diseases should be revisited (7). However, although the results presented come from a representative mouse model, studies in humans are required to confirm the hypothesis that CD8 ϩ T cells are involved in the development of AD skin lesions.…”

Section: Discussionsupporting

confidence: 92%

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Hennino

Vocanson

Toussaint

et al. 2007

The Journal of Immunology

103

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Skin lesions in the allergic form of atopic dermatitis (AD) are induced by allergen-specific T cells that infiltrate the skin at the site of allergen exposure. Although Th2-type CD4+ T cells appear to be crucial in AD pathophysiology, little is known about the contribution of CD8+ T cells in the development of the allergic skin inflammation. In the present study, we have analyzed the respective role of CD8+ and CD4+ T cells in the development of AD skin lesions in a mouse model of allergen-induced AD. In sensitized mice, CD8+ T cells are rapidly and transiently recruited to the allergen-exposed site and initiate the inflammatory process leading to skin infiltration with eosinophils and Th1/Th2-producing cells. CD8+ T cell-depleted mice show no inflammation, demonstrating that these cells are mandatory for the development of AD. In contrast, CD4+ T cell-depleted mice develop a severe form of eczema. Furthermore, adoptive transfer of CD8+ T cells from sensitized mice into naive recipient mice leads to skin inflammation soon after allergen exposure. These data indicate that allergen-primed CD8+ T cells are required for the development of AD-like lesions in mice.

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Section: Discussionsupporting

confidence: 92%

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Hennino

Vocanson

Toussaint

et al. 2007

The Journal of Immunology

103

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“…The effects of this cytokine are broad, including mucus production, increased responsiveness of airway smooth muscle to acetylcholine, and secretion of matrix metalloproteases and cysteine proteases, involved in lung remodeling. It was recently shown that IL-13 alone from CD8 + T cells was sufficient to cause AHR in OVA-sensitized mice [33,34]. The present data suggest that it is a combination of IL-13 and IL-4 from CD8 cells that mediate an airway response.…”

Section: Discussionsupporting

confidence: 63%

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

et al. 2005

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The pathogenesis of asthma has been linked to the production of type 2 cytokines, which can be expressed by several cell types in the lung. These studies investigated CD8 + T cell responses in a murine cockroach antigen (CRA) model of asthma. The results from these present studies show that depletion of CD8 + T cells after allergen sensitization to CRA significantly reduces airway hyperreactivity, airway eosinophilia and pulmonary type 2 cytokine levels. The data demonstrate that CD8 + T cells from CRA-sensitized mice can produce type 2 cytokines IL-4, IL-5 and IL-13 upon antigen challenge, and that the transfer of these cells into naive mice will cause airway hyperreactivity when exposed to CRA. We found that the transferred airway response is dependent on both IL-4 and IL-13 from CD8 + T cells using cytokine knockout mice. Compared to CD4 + T cells, CD8 + T cells were not as numerous in the lungs of sensitized and challenged mice, but were as efficacious in the transfer of airway disease. The most severe airway response was observed when both CD4 + and CD8 + T cells were transferred at the same time. Altogether, these studies highlight a role for CD8 + T lymphocytes in the development of allergen-induced airway responses.

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“…PE-conjugated anti-mouse Gr-1 and allophycocyanin-conjugated CD11c were used to identify plasmacytoid DCs. The stained cells were washed, resuspended in PBS, and then analyzed by flow cytometry (FACSCalibur) as previously described (32). The numbers of CD11c ϩ and CFSE ϩ cells in BAL, PBLN, and lungs were derived by multiplying the percentage of stained cells by the total number of cells isolated.…”

Section: Flow Cytometrymentioning

confidence: 99%

Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness

Miyahara

Ohnishi

Matsuda

et al. 2008

The Journal of Immunology

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Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B4 (LTB4), interacting with its high-affinity receptor, LTB4 receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161–167). However, the role for the LTB4-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1−/−) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1−/− BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1−/− BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1−/− BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1+/+ BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.

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Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13

Cited by 102 publications

References 61 publications

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness

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