Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells.
In the present study, we show that IL-2, IL-4, IL-7, and IL-15 are able to induce functional CXCR4 surface expression on resting in vitro-generated CD4+ CXCR4- CCR7+ memory T cells. Cytokine-mediated induction of CXCR4 expression was associated with an increase in CXCR4 transcription, enhanced stromal-derived factor-1-induced T cell migration in vitro, and increased susceptibility of these cells to infection with X4 strains of HIV-1. CXCR4 expression could also be induced through an alternative pathway, following coculture of these cells with CD40-activated, autologous, CD34+ progenitor-derived dendritic cells. Although these dendritic cells express transcripts for IL-7 and IL-15, addition of neutralizing anti-IL-7R and IL-15 mAbs did not block induction of CXCR4 expression. Indeed, dendritic cell-mediated up-regulation of CXCR4 expression was found to depend on CD40/CD154 and CD134/CD134L interactions. Whereas activated autologous dendritic cells induced the expression of both CXCR4 and CD25 on a portion of CCR7+ memory T cells, concomitant CD3-mediated activation of these cells further enhanced CD25 expression, but, in contrast, prevented induction of CXCR4 expression. This observation suggests that triggering of the CD134 and CD154 molecules, in contrast to TCR/CD3 complex-mediated stimulation, results in simultaneous T cell activation and CXCR4 expression. Taken together, these results show that common gamma-chain-interacting cytokines as well as signals mediated via noncognate interactions between activated dendritic cells and memory T cells are involved in the up-regulation of CXCR4 expression.
Jourdan
P
P
Institut National de la Santé et de la Recherche Médicale Unite 454, Montpellier, France.
Vendrell
J P
JP
Huguet
M F
MF
Segondy
M
M
Bousquet
J
J
Pène
J
J
Yssel
H
H
D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000097:blood; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002465:Cell Movement / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D005312:Fetal Blood / Q000166:cytology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000097:blood; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000097:blood; D018121:Receptors, Cytokine / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
C515370:CCR7 protein, human; D017252:CD3 Complex; D015704:CD4 Antigens; D019013:CD40 Antigens; C515255:CXCL12 protein, human; C515371:Ccr7 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand; D015847:Interleukin-4; D017493:Leukocyte Common Antigens