Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.

Abstract

BACKGROUND:

Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity.

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.

• 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)
• 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

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)