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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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(a) Chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2)+ T cells in bronchoalveolar lavage (BAL) from asthmatic (•) and normal (▴) subjects. There was a significant difference between asthmatic and normal controls. *P < 0·05 using the Mann–Whitney U-test. Bars represent mean percentages. (b) CRTH2+ T cells in paired blood (□) and BAL (▵) samples from normal subjects. Lines connect samples from the same subject. *P < 0·05 using the Mann–Whitney U-test.
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fig03: (a) Chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2)+ T cells in bronchoalveolar lavage (BAL) from asthmatic (•) and normal (▴) subjects. There was a significant difference between asthmatic and normal controls. *P < 0·05 using the Mann–Whitney U-test. Bars represent mean percentages. (b) CRTH2+ T cells in paired blood (□) and BAL (▵) samples from normal subjects. Lines connect samples from the same subject. *P < 0·05 using the Mann–Whitney U-test.

Mentions: Although BAL was taken from 12 asthma subjects, one sample had be eliminated due to very poor quality and non-specific staining. There was only a small number of CRTH2+ T cells in the BAL in both groups. Nevertheless, there was a significant difference between the two groups (2·3% ± 0·6 in asthmatics versus 0·3% ± 0·1 in normal subjects; P < 0·05) (Fig. 3a). We also compared the percentages of CRTH2+ T cells in paired blood and BAL samples from the same subject. No significant difference was seen in asthmatics; however, there was a significant difference in normal subjects (0·8% ± 0·1 in blood versus 0·3% ± 0·1 in BAL; P < 0·05) (Fig. 3b).


CRTH2 expression on T cells in asthma.

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

(a) Chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2)+ T cells in bronchoalveolar lavage (BAL) from asthmatic (•) and normal (▴) subjects. There was a significant difference between asthmatic and normal controls. *P < 0·05 using the Mann–Whitney U-test. Bars represent mean percentages. (b) CRTH2+ T cells in paired blood (□) and BAL (▵) samples from normal subjects. Lines connect samples from the same subject. *P < 0·05 using the Mann–Whitney U-test.
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Related In: Results  -  Collection

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

fig03: (a) Chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2)+ T cells in bronchoalveolar lavage (BAL) from asthmatic (•) and normal (▴) subjects. There was a significant difference between asthmatic and normal controls. *P < 0·05 using the Mann–Whitney U-test. Bars represent mean percentages. (b) CRTH2+ T cells in paired blood (□) and BAL (▵) samples from normal subjects. Lines connect samples from the same subject. *P < 0·05 using the Mann–Whitney U-test.
Mentions: Although BAL was taken from 12 asthma subjects, one sample had be eliminated due to very poor quality and non-specific staining. There was only a small number of CRTH2+ T cells in the BAL in both groups. Nevertheless, there was a significant difference between the two groups (2·3% ± 0·6 in asthmatics versus 0·3% ± 0·1 in normal subjects; P < 0·05) (Fig. 3a). We also compared the percentages of CRTH2+ T cells in paired blood and BAL samples from the same subject. No significant difference was seen in asthmatics; however, there was a significant difference in normal subjects (0·8% ± 0·1 in blood versus 0·3% ± 0·1 in BAL; P < 0·05) (Fig. 3b).

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