Abstract | BACKGROUND: OBJECTIVE: To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma. METHODS: CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with anti-CD3/anti-CD28 followed by analysis of BLT1 surface expression and cytokine production. Activation of CD8(+) T cells after ligation of BLT1 by LTB4 was monitored by changes in intracellular Ca(2+) concentrations. RESULTS: The number of BLT1-expressing cells was larger in patients with asthma than in controls and larger on activated CD8(+) than on CD4(+) T cells. Addition of LTB4 to activated CD8(+) T cells resulted in increases in intracellular Ca(2+) concentrations. Expansion of activated CD4(+) T cells, unlike CD8(+) T cells, was significantly decreased in the presence of corticosteroid. In patients with SS asthma, numbers of BLT1-expressing CD8(+) T cells were lower in the presence of corticosteroid, unlike in those with SR asthma in whom cell expansion was maintained. Levels of interleukin-13 were highest in cultured CD8(+) T cells, whereas interleukin-10 levels were higher in CD4(+) T cells from controls and patients with SS asthma. Interferon-γ levels were lowest in patients with SR asthma. CONCLUSION: Differences in BLT1 expression, steroid sensitivity, and cytokine production were demonstrated in T lymphocytes from patients with SS and SR asthma. The LTB4-BLT1 pathway in CD8(+) cells may play an important role in asthma and serve as an important target in the treatment of patients with SR asthma.
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Authors | Eun Hee Chung, Yi Jia, Hiroshi Ohnishi, Katsuyuki Takeda, Donald Y M Leung, E Rand Sutherland, Azzeddine Dakhama, Richard J Martin, Erwin W Gelfand |
Journal | Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
(Ann Allergy Asthma Immunol)
Vol. 112
Issue 3
Pg. 211-216.e1
(Mar 2014)
ISSN: 1534-4436 [Electronic] United States |
PMID | 24428972
(Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Adrenal Cortex Hormones
- Antibodies, Monoclonal
- CD28 Antigens
- CD3 Complex
- Culture Media, Conditioned
- IL10 protein, human
- Interleukin-13
- LTB4R protein, human
- Receptors, Leukotriene B4
- Interleukin-10
- Dexamethasone
- Interferon-gamma
- Calcium
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Topics |
- Adrenal Cortex Hormones
(pharmacology)
- Adult
- Antibodies, Monoclonal
(immunology)
- Asthma
(immunology)
- CD28 Antigens
(immunology)
- CD3 Complex
(immunology)
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Calcium
(metabolism)
- Cells, Cultured
- Culture Media, Conditioned
(chemistry)
- Dexamethasone
(pharmacology)
- Female
- Humans
- Interferon-gamma
(metabolism)
- Interleukin-10
(metabolism)
- Interleukin-13
(metabolism)
- Lymphocyte Activation
(immunology)
- Male
- Receptors, Leukotriene B4
(metabolism)
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