T cell expression of CXCR1 is a marker of atopic allergy and is downregulated following grass pollen immunotherapy

Abstract

Rationale In allergic rhinitis, recruitment of Th2 cells to the nasal mucosa may be directed by distinct profiles of chemokine receptor (CKR) expression. We previously examined CKR expression (CCR1-7 and CXCR1-4) on peripheral T cells from atopic rhinitics compared with healthy controls (JACI, Vol 109, pS62, A143, 2002). Only CXCR1+CD4+ cells were increased in atopic donors. Methods CXCR1 expression was measured by flow cytometry on freshly isolated PBMC and on T cell lines derived from nasal biopsies and PBMC. Normal donors, grass sensitive rhinitics, and subjects who have received successful grass pollen immunotherapy (IT) were compared. Results On fresh cells, atopic individuals exhibited increased numbers of CXCR1+CD4+ cells compared to normals (p=0.018). Functionally, CXCR1+ T cells from atopic donors showed an enhanced actin polymerization response after stimulation with its ligand, CXCL8. IFNγ expression was lower in CXCR1+CD4+ cells and numbers of CXCR1+ cells were upregulated in the presence of the pro-allergic cytokine, IL-4. T cell lines derived from both nasal tissue and peripheral blood also revealed significant increases in CXCR1 expression by atopic donors compared to normal subjects (nose: Normal 2.9 ± 0.75 (mean ± SE), Atopic, 8.3 ± 2.1; p=0.021; blood: Normal, 3.7 ± 1.3, Atopic 7.7 ± 0.6; p=0.015). CXCR1 expression on freshly isolated PBMC (Atopic 9.4 ± 1.4, IT 3.4 ± 0.6; p=0.004), cultured cells from the nose (Atopic 10.0 ± 2.5, IT 1.8 ± 0.6; p=0.01) and blood (Atopic 8.0 ± .05, IT 3.5 ± 0.7; p=0.005) was decreased in patients (n=8-11) undergoing grass pollen immunotherapy. Conclusion CXCR1 is a marker of atopic allergy which is downregulated by specific immunotherapy. CXCR1 represents a potential target for therapeutic intervention.