Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.

Krinzman, Stephen J.; Sanctis, George T. De; Cernadas, Manuela; Mark, David A.; Wang, Y; Listman, James A.; Kobzik, Lester; Donovan, Carolyn E.; Nassr, K; Katona, I M; Christiani, David C.; Perkins, David L.; Finn, Patricia W.

doi:10.1172/jci119093

Cited by 129 publications

(91 citation statements)

References 34 publications

(38 reference statements)

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“…In several studies, CD28 blockade has led to significant and clinically relevant modulation of inflammatory diseases (17)(18)(19)(20)(21)(22)(23)(24). Besides reduced T cell infiltration, some of these studies have reported a diminished tissue PMN Ϫ recruitment (19,20,23,24).…”

Section: Discussionmentioning

confidence: 99%

“…Blockade of CD28 signals by antibodies or by generation of CD28 gene-deficient mice caused attenuated inflammatory responses in several (experimental) diseases, including contact hypersensitivity (17), graft-versus-host disease (18), psoriasis (19), bleomycin-induced lung fibrosis (20), and asthma (21). Moreover, antibody blockade of CD28 signals during murine septic shock drastically improved survival rate.…”

mentioning

confidence: 99%

See 1 more Smart Citation

T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia

Singbartl

Bockhorn

Zarbock

et al. 2005

Journal of the American Society of Nephrology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia

Singbartl

Bockhorn

Zarbock

et al. 2005

Journal of the American Society of Nephrology

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“…Although there is a significant amount of data suggesting that CD28 may preferentially affect the differentiation to T H 2 cells in vitro (12,13), as well as in vivo (11,14), this remains an unclarified point because there are reports of CD28-independent T H 2 responses in vitro (15) and in vivo (16). Whether CD28 signals affect the ability of T cells to develop into T H 2 cells or their subsequent secretion of cytokine is not clear; however, CD28 signals have been demonstrated to be required for the development of allergic asthma in mice (17)(18)(19)(20)(21). The CD28 related costimulatory molecule inducible costimulator molecule has also been demonstrated to be involved in regulating the pathology of either a Shistosoma mansoni model of allergic airway disease (22) or an OVA model of asthma in mice (23).…”

mentioning

confidence: 99%

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

Mueller

August

2003

The Journal of Immunology

147

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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“…Briefly, mice were sensitized by intraperitoneal injection with 10 g chicken OVA and 1 mg Al(OH) 3 (alum) on Days 0 and 7. On Days 14-20, mice received aerosolized OVA challenge with 6% OVA for 20 min/d.…”

Section: Protocol For Allergen Sensitization and Challengementioning

confidence: 99%

“…In addition, costimulatory molecules on the T cell and antigen-presenting cell interact for complete T-cell activation. Pathways involving the costimulatory molecules CD28 and CD80/86 are the best-described costimulatory interactions and have been shown to play an important role in the pathogenesis of allergic asthma in murine models (1)(2)(3)(4). These costimulatory molecules may be only partially responsible for allergic responses because blocking or deficiency of these molecules does not equally affect all allergic parameters.…”

mentioning

confidence: 99%

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

Wang

Campo²,

Ting³

et al. 2006

Am J Respir Cell Mol Biol

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T-cell activation plays an essential role in the generation of the pulmonary inflammation that is manifest in allergic asthma. Optimal T-cell activation requires not only presentation of antigen with the major histocompatibility complex, but also concurrent signaling through costimulatory molecules. The costimulatory molecule SLAM (Signaling Lymphocytic Activation Molecule, CD150) is a glycoprotein expressed on activated lymphocytes and antigenpresenting cells. Disruption of the SLAM gene demonstrated that SLAM-induced signal transduction pathways regulate cytokine production by T helper (Th)2 cells and macrophages. Here we tested the postulate that the costimulatory molecule SLAM may be critical for allergic inflammation in a murine model. SLAM-deficient mice did not manifest allergen-induced bronchoalveolar lavage eosinophilia, increased serum IgE, or heightened airway responses compared with wild-type mice. Allergen-induced Th2 cytokines and Th1 cytokines were decreased in SLAM-deficient mice. These data support the concept that SLAM plays a crucial role in allergic responses.

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Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.

Cited by 129 publications

References 34 publications

T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia

T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia

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

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

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