CXCR1+CD4+ T cells in human allergic disease.
Chemokine receptors play an important role in the migration of leukocytes to sites of allergic inflammation in humans. In this study, we have identified increased expression of the chemokine receptor CXCR1 on CD4+ T lymphocytes derived from patients with atopic disease compared with normal donors. Enhanced expression of CXCR1 by atopic donors was identified on freshly isolated peripheral blood cells and on expanded cell populations derived from nasal mucosal biopsies and from the periphery. Identification of CXCR1 expression on CD4 cells in the nasal mucosa was confirmed by double immunofluorescence. In addition, expression of CXCR1 was dramatically decreased in patients undergoing successful treatment of allergic rhinitis by specific immunotherapy. CXCR1 provided a functional receptor capable of regulating T cells in the context of allergic disease, since expression of CXC chemokine ligand 8 was up-regulated at the site of allergic inflammation and freshly isolated CXCR1+CD4+ cells from atopic donors showed an enhanced functional response to this ligand. CXCR1 expression on CD4+ T cells was increased in vitro in response to the pro-Th2 cytokine IL-4. Phenotypic analysis reveals that IFN-gamma expression was lower in the CXCR1+CD4+ cells. The identification of CXCR1 as a marker of allergic rhinitis reveals a possible target for therapeutic intervention in atopic disease.
Francis
James N
JN
Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, United Kingdom.
Jacobson
Mikila R
MR
Lloyd
Clare M
CM
Sabroe
Ian
I
Durham
Stephen R
SR
Till
Stephen J
SJ
D000485:Allergens / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D018655:Lymphocyte Count; D009297:Nasal Mucosa / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis* / Q000097:blood; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000485:Allergens; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D023062:Receptors, Interleukin-8A; D015847:Interleukin-4