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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) Scatter-plot showing chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2) expression on (♦) interferon (IFN)-γ+, (•) interleukin (IL)-4+ and (▴) IL-13+ T cells derived from peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Cells were stimulated for 6 h with phorbol myristate acetate (PMA) and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages. (b) Scatter-plot showing CRTH2 expression on (♦) IFN-γ+, (•) IL-4+ and (▴) IL-13+ T cells derived from PBMC from normal subjects. Cells were stimulated for 6 h with PMA and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages.
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fig02: (a) Scatter-plot showing chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2) expression on (♦) interferon (IFN)-γ+, (•) interleukin (IL)-4+ and (▴) IL-13+ T cells derived from peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Cells were stimulated for 6 h with phorbol myristate acetate (PMA) and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages. (b) Scatter-plot showing CRTH2 expression on (♦) IFN-γ+, (•) IL-4+ and (▴) IL-13+ T cells derived from PBMC from normal subjects. Cells were stimulated for 6 h with PMA and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages.

Mentions: The association of blood T cell CRTH2 expression with intracellular cytokine was studied following in vitro stimulation of PBMC with PMA and calcium ionophore for 6 h. CRTH2 was expressed by a higher percentage of IL-4+ and IL-13+ T cells than IFN-γ+ T cells. In asthma, 26·5% ± 4·5 and 35·5% ± 3·3 of the IL-4+- and IL-13+-producing T cells also expressed CRTH2, while only 2·4% ± 0·5 of IFN-γ+ cells also expressed CRTH2 (P < 0·001) (Fig. 2a). A similar pattern of expression of CRTH2 on IL-4+ and IL-13+ T cells relative to IFN-γ+ T cells was also seen in blood of normal subjects (Fig. 2b).


CRTH2 expression on T cells in asthma.

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

(a) Scatter-plot showing chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2) expression on (♦) interferon (IFN)-γ+, (•) interleukin (IL)-4+ and (▴) IL-13+ T cells derived from peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Cells were stimulated for 6 h with phorbol myristate acetate (PMA) and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages. (b) Scatter-plot showing CRTH2 expression on (♦) IFN-γ+, (•) IL-4+ and (▴) IL-13+ T cells derived from PBMC from normal subjects. Cells were stimulated for 6 h with PMA and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages.
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Related In: Results  -  Collection

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

fig02: (a) Scatter-plot showing chemokine receptor homologous molecule expressed on T helper type 2 (Th2) lymphocytes (CRTH2) expression on (♦) interferon (IFN)-γ+, (•) interleukin (IL)-4+ and (▴) IL-13+ T cells derived from peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Cells were stimulated for 6 h with phorbol myristate acetate (PMA) and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages. (b) Scatter-plot showing CRTH2 expression on (♦) IFN-γ+, (•) IL-4+ and (▴) IL-13+ T cells derived from PBMC from normal subjects. Cells were stimulated for 6 h with PMA and calcium ionophore. ***P < 0·001 using the Mann–Whitney U-test. Bars represent mean percentages.
Mentions: The association of blood T cell CRTH2 expression with intracellular cytokine was studied following in vitro stimulation of PBMC with PMA and calcium ionophore for 6 h. CRTH2 was expressed by a higher percentage of IL-4+ and IL-13+ T cells than IFN-γ+ T cells. In asthma, 26·5% ± 4·5 and 35·5% ± 3·3 of the IL-4+- and IL-13+-producing T cells also expressed CRTH2, while only 2·4% ± 0·5 of IFN-γ+ cells also expressed CRTH2 (P < 0·001) (Fig. 2a). A similar pattern of expression of CRTH2 on IL-4+ and IL-13+ T cells relative to IFN-γ+ T cells was also seen in blood of normal subjects (Fig. 2b).

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