CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway

Kathrin Gollmer, François Asperti-Boursin, Yoshihiko Tanaka, Klaus Okkenhaug, Bart Vanhaesebroeck, Jeffrey R. Peterson, Yoshinori Fukui, Emmanuel Donnadieu, Jens V. Stein

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

CD4+ T cells use the chemokine receptor CCR7 to home to and migrate within lymphoid tissue, where T-cell activation takes place. Using primary T-cell receptor (TCR)-transgenic (tg) CD4+ T cells, we explored the effect of CCR7 ligands, in particular CCL21, on T-cell activation. We found that the presence of CCL21 during early time points strongly increased in vitro T-cell proliferation after TCR stimulation, correlating with increased expression of early activation markers. CCL21 costimulation resulted in increased Ras- and Rac-GTP formation and enhanced phosphorylation of Akt, MEK, and ERK but not p38 or JNK. Kinase-dead PI3KδD910A/D910A or PI3Kγ-deficient TCR-tg CD4+ T cells showed similar responsiveness to CCL21 costimulation as control CD4+ T cells. Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4+ T cells, concomitant with impaired Rac- but not Ras-GTP formation. Using lymph node slices for live monitoring of T-cell behavior and activation, we found that G proteincoupled receptor signaling was required for early CD69 expression but not for Ca2+ signaling. Our data suggest that the presence of CCL21 during early TCR signaling lowers the activation threshold through Ras- and Rac-dependent pathways leading to increased ERK phosphorylation.

Original languageEnglish
Pages (from-to)580-588
Number of pages9
JournalBlood
Volume114
Issue number3
DOIs
Publication statusPublished - Nov 20 2009

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T-cells
T-Lymphocytes
T-Cell Antigen Receptor
Chemical activation
Phosphorylation
Guanosine Triphosphate
Chemokine Receptors
Mitogen-Activated Protein Kinase Kinases
Cell proliferation
Guanine
Lymphoid Tissue
Phosphatidylinositol 3-Kinases
Phosphotransferases
Lymph Nodes
Cell Proliferation
Tissue
Ligands
Monitoring

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Gollmer, K., Asperti-Boursin, F., Tanaka, Y., Okkenhaug, K., Vanhaesebroeck, B., Peterson, J. R., ... Stein, J. V. (2009). CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood, 114(3), 580-588. https://doi.org/10.1182/blood-2009-01-200923

CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. / Gollmer, Kathrin; Asperti-Boursin, François; Tanaka, Yoshihiko; Okkenhaug, Klaus; Vanhaesebroeck, Bart; Peterson, Jeffrey R.; Fukui, Yoshinori; Donnadieu, Emmanuel; Stein, Jens V.

In: Blood, Vol. 114, No. 3, 20.11.2009, p. 580-588.

Research output: Contribution to journalArticle

Gollmer, K, Asperti-Boursin, F, Tanaka, Y, Okkenhaug, K, Vanhaesebroeck, B, Peterson, JR, Fukui, Y, Donnadieu, E & Stein, JV 2009, 'CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway', Blood, vol. 114, no. 3, pp. 580-588. https://doi.org/10.1182/blood-2009-01-200923
Gollmer K, Asperti-Boursin F, Tanaka Y, Okkenhaug K, Vanhaesebroeck B, Peterson JR et al. CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood. 2009 Nov 20;114(3):580-588. https://doi.org/10.1182/blood-2009-01-200923
Gollmer, Kathrin ; Asperti-Boursin, François ; Tanaka, Yoshihiko ; Okkenhaug, Klaus ; Vanhaesebroeck, Bart ; Peterson, Jeffrey R. ; Fukui, Yoshinori ; Donnadieu, Emmanuel ; Stein, Jens V. / CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway. In: Blood. 2009 ; Vol. 114, No. 3. pp. 580-588.
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