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CRTH2 expression on T cells in asthma.

Mutalithas K, Guillen C, Day C, Brightling CE, Pavord ID, Wardlaw AJ - Clin. Exp. Immunol. (2010)

Bottom Line: PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro.CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-gamma+ T cells (P<0.001).CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-gamma+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Institute for Lung Health, Department of Infection Immunity and Inflammation, University Hospitals of Leicester, Leicester, UK.

ABSTRACT
Mast cell-derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G-protein-coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1.8%+/-0.2) and normal (1.6%+/-0.2) subjects. CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-gamma+ T cells (P<0.001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2.3%+/-0.6) and normal subjects (0.3%+/-0.1), and there was a significant difference between the two groups (P<0.05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood-BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL-4+ and IL-13+ T cells compared to IFN-gamma+ T cells was also seen in BAL from asthmatics (P<0.001). CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-gamma+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung.

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Levels of prostaglandin D2 (PGD2) in bronchoalveolar lavage (BAL) fluid from asthmatic (□) and normal subjects (▴). Bars represent mean percentages. No significant difference was seen between the two groups.
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fig05: Levels of prostaglandin D2 (PGD2) in bronchoalveolar lavage (BAL) fluid from asthmatic (□) and normal subjects (▴). Bars represent mean percentages. No significant difference was seen between the two groups.

Mentions: Although there was no difference in the percentage of CRTH2+ T cells between BAL and blood in asthma, there was a higher percentage of these cells in asthmatic BAL compared to normal controls. We have therefore measured the ligand for CRTH2, PGD2 in BAL. Although a significant difference was not seen between the two groups, a bimodal distribution of PGD2 levels was seen within the asthma group (Fig. 5). A similar distribution was seen with CRTH2+ T cells in BAL in asthma (Fig. 3a). We therefore explored whether there was a correlation between the percentages of CRTH2+ T cells and PGD2 within the same BAL sample. Due to the small numbers, Spearman's correlation test was used. A significant correlation was not seen (r2 = 0·4; P = 0·07).


CRTH2 expression on T cells in asthma.

Mutalithas K, Guillen C, Day C, Brightling CE, Pavord ID, Wardlaw AJ - Clin. Exp. Immunol. (2010)

Levels of prostaglandin D2 (PGD2) in bronchoalveolar lavage (BAL) fluid from asthmatic (□) and normal subjects (▴). Bars represent mean percentages. No significant difference was seen between the two groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901512&req=5

fig05: Levels of prostaglandin D2 (PGD2) in bronchoalveolar lavage (BAL) fluid from asthmatic (□) and normal subjects (▴). Bars represent mean percentages. No significant difference was seen between the two groups.
Mentions: Although there was no difference in the percentage of CRTH2+ T cells between BAL and blood in asthma, there was a higher percentage of these cells in asthmatic BAL compared to normal controls. We have therefore measured the ligand for CRTH2, PGD2 in BAL. Although a significant difference was not seen between the two groups, a bimodal distribution of PGD2 levels was seen within the asthma group (Fig. 5). A similar distribution was seen with CRTH2+ T cells in BAL in asthma (Fig. 3a). We therefore explored whether there was a correlation between the percentages of CRTH2+ T cells and PGD2 within the same BAL sample. Due to the small numbers, Spearman's correlation test was used. A significant correlation was not seen (r2 = 0·4; P = 0·07).

Bottom Line: PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro.CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-gamma+ T cells (P<0.001).CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-gamma+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Institute for Lung Health, Department of Infection Immunity and Inflammation, University Hospitals of Leicester, Leicester, UK.

ABSTRACT
Mast cell-derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G-protein-coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1.8%+/-0.2) and normal (1.6%+/-0.2) subjects. CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-gamma+ T cells (P<0.001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2.3%+/-0.6) and normal subjects (0.3%+/-0.1), and there was a significant difference between the two groups (P<0.05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood-BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL-4+ and IL-13+ T cells compared to IFN-gamma+ T cells was also seen in BAL from asthmatics (P<0.001). CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-gamma+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung.

Show MeSH
Related in: MedlinePlus