Eotaxin activates T cells to chemotaxis and adhesion only if induced to express CCR3 by IL-2 together with IL-4.
The transmigration and adherence of T lymphocytes through microvascular endothelium are essential events for their recruitment into inflammatory sites. In the present study, we investigated the expression of CC chemokine receptor CCR3 on T lymphocytes and the capacities of the CC chemokine eotaxin to induce chemotaxis and adhesion in T lymphocytes. We have observed a novel phenomenon that IL-2 and IL-4 induce the expression of CCR3 on T lymphocytes. We also report that CC chemokine eotaxin is a potent chemoattractant for IL-2- and IL-4-stimulated T lymphocytes, but not for freshly isolated T lymphocytes. Eotaxin attracts T lymphocytes via CCR3, documented by the fact that anti-CCR3 mAb blocks eotaxin-mediated T lymphocyte chemotaxis. In combination with IL-2 and IL-4, eotaxin enhances the expression of adhesion molecules such as ICAM-1 and several integrins (CD29, CD49a, and CD49b) on T lymphocytes and thus promotes adhesion and aggregation of T lymphocytes. The eotaxin-induced T lymphocyte adhesion could be selectively blocked by a specific cAMP-dependent protein kinase inhibitor, H-89, indicating that eotaxin activates T lymphocytes via a special cAMP-signaling pathway. Our new findings all point toward the fact that eotaxin, in association with the Th1-derived cytokine IL-2 and the Th2-derived cytokine IL-4, is an important T lymphocyte activator, stimulating the directional migration, adhesion, accumulation, and recruitment of T lymphocytes, and paralleled the accumulation of eosinophils and basophils during the process of certain types of inflammation such as allergy.
Jinquan
T
T
Department of Dermatology, University Marselisborg Hospital, Aarhus University, Denmark. TAN@RH.DK
Quan
S
S
Feili
G
G
Larsen
C G
CG
Thestrup-Pedersen
K
K
D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D000242:Cyclic AMP / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D004357:Drug Synergism; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D016023:Integrins; D007376:Interleukin-2; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D000242:Cyclic AMP