Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells.
Polarized Th1 and Th2 cells differentially express adhesion molecules and chemokine receptors, endowing these cells with distinct tissue homing capabilities. Here we report that, in contrast to other chemokine receptors, the expression of CCR4 and CCR8 on Th2 cells is transiently increased following TCR and CD28 engagement. IL-4 is not required for this activation-induced up-regulation of CCR4 and CCR8. In accordance with receptor expression, the response of Th2 cells to I-309 (CCR8 ligand) and thymus- and activation-regulated chemokine (CCR4 and CCR8 ligand) is enhanced upon activation. Moreover, activated Th1 cells up-regulate CCR4 expression and functional responsiveness to thymus- and activation-regulated chemokine. Analysis of polarized subsets of CD8+ T cells reveals a similar pattern of chemokine receptor expression and modulation of responsiveness. Taken together, these findings suggest that an up-regulation of CCR4 and CCR8 following Ag encounter may contribute to the proper positioning of activated T cells within sites of antigenic challenge and/or specialized areas of lymphoid tissues.
D'Ambrosio
D
D
Roche Milano Ricerche, Milan, Italy. daniele.dambrosio@roche.com
Iellem
A
A
Bonecchi
R
R
Mazzeo
D
D
Sozzani
S
S
Mantovani
A
A
Sinigaglia
F
F
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D002999:Clone Cells; D005312:Fetal Blood; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation; D054398:Receptors, CCR4; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
C515354:CCR4 protein, human; C103330:CCR8 protein, human; D054398:Receptors, CCR4; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D002118:Calcium