Kinetics and expression patterns of chemokine receptors in human CD4+ T lymphocytes primed by myeloid or plasmacytoid dendritic cells.
We investigated the kinetics of expression of 12 chemoattractant receptors as a function of cell division following priming of human naive CD4+ T cells by different populations of dendritic cells (DC) and under conditions favoring Th1 or Th2 differentiation. Two chemokine receptors, CXCR3 and CXCR5, were rapidly up-regulated following T cell activation by either monocyte-derived DC, myeloid DC (mDC) or plasmacytoid DC (pDC). While CXCR5 expression was transient, expression of CXCR3 at advanced cell divisions was dependent on differentiation, being expressed at high levels on Th1 cells. Several other receptors (CCR2, CCR3, CCR4, CCR5, CXCR6 and CRTh2) were acquired progressively as a function of cell division and in a fashion that was influenced by polarizing cytokines. The Th2-associated chemoattractant receptors CRTh2 and CCR3 were up-regulated with slower kinetics compared to the Th1-associated receptors CXCR3 and CXCR6, consistent with a different kinetics and efficiency of polarization. Moreover, CCR4 and CXCR6 were preferentially induced in T cells activated by mDC and pDC, respectively. Finally, CXCR5 and CCR7 were also rapidly and transiently up-regulated in memory T cells following TCR stimulation. These results indicate a complex chemokine receptor regulation dependent on both T cell activation and differentiation state. In addition, they reveal the existence of DC-specific cues for the regulation of T cell migratory capacity.
Langenkamp
Anja
A
Institute for Research in Biomedicine, Bellinzona, Switzerland.
Nagata
Kinya
K
Murphy
Kristine
K
Wu
Lijun
L
Lanzavecchia
Antonio
A
Sallusto
Federica
F
D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D018899:CpG Islands; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D011982:Receptors, Prostaglandin; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
C515334:CCR2 protein, human; C515350:CCR3 protein, human; C515354:CCR4 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human; C095085:CXCR5 protein, human; D008070:Lipopolysaccharides; D011948:Receptors, Antigen, T-Cell; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor