FUNCTIONAL EXPRESSION OF THE EOTAXIN RECEPTOR CCR3 IN T-LYMPHOCYTES CO-LOCALIZING WITH EOSINOPHILS

Background: The chemokine eotaxin is produced at sites of allergic inf lammation, binds selectively to the chemokine receptor CCR3 and attrac ts eosinophil and basophil leukocytes, which express high numbers of t his receptor. Responses of T lymphocytes to eotaxin have not been repo rted so far. We have investigated the expression of CCR3 in T lymphocy tes and analysed the properties and in vivo distribution of T lymphocy tes expressing this receptor. Results: In search of chemokine receptor s with selective expression in T lymphocytes, we have isolated multipl e complementary DNAs (cDNAs) encoding CCR3 from a human CD4(+) T-cell cDNA library. T-lymphocyte clones with selectivities for protein and n on-protein antigens were analysed for expression of CCR3 and productio n of Th1- and Th2-type cytokines. Of 13 clones with surface CCR3, nine secreted enhanced levels of interleukin-4 and/or interleukin-5, indic ating that CCR3 predominates in Th2-type lymphocytes, CCR3(+) T lympho cytes readily migrated in response to eotaxin, and showed the characte ristic changes in cytosolic free calcium. Immunostaining of contact de rmatitis, nasal polyp and ulcerative colitis tissue showed that CCR3() T lymphocytes are recruited together with eosinophils and, as assess ed by flow cytometry, a large proportion of CD3(+) cells extracted fro m the inflamed skin tissue were CCR3(+). By contrast, CCR3(+) T lympho cytes were absent from tissues that lack eosinophils, as demonstrated for normal skin and rheumatoid arthritis synovium. Conclusions: We sho w that T lymphocytes co-localizing with eosinophils at sites of allerg ic inflammation express CCR3, suggesting that eotaxin/CCR3 represents a novel mechanism of T-lymphocyte recruitment. These cells are essenti al in allergic inflammation, as mice lacking mature T lymphocytes were insensitive to allergen challenge. Surface CCR3 may mark a subset of T lymphocytes that induce eosinophil mobilization and activation throu gh local production of Th2-type cytokines.