Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration

Jacob D. Estes, Tyler C. Thacker, Denise L. Hampton, Sariah A. Kell, Brandon F. Keele, Emily A. Palenske, Kirk M. Druey, Gregory F. Burton

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Follicular dendritic cells (FDCs) up-regulate the chemokine receptor CXCR4 on CD4 T cells, and a major subpopulation of germinal center (GC) T cells (CD4+CD57+), which are adjacent to FDCs in vivo, expresses high levels of CXCR4. We therefore reasoned that GC T cells would actively migrate to stromal cell-derived factor-1 (CXCL12), the CXCR4 ligand, and tested this using Transwell migration assays with GC T cells and other CD4 T cells (CD57-) that expressed much lower levels of CXCR4. Unexpectedly, GC T cells were virtually nonresponsive to CXCL12, whereas CD57-CD4 T cells migrated efficiently despite reduced CXCR4 expression. In contrast, GC T cells efficiently migrated to B cell chemoattractant-1/CXCL13 and FDC supernatant, which contained CXCL13 produced by FDCs. Importantly, GC T cell nonresponsiveness to CXCL12 correlated with high ex vivo expression of regulator of G protean signaling (RGS), RGS13 and RGS16, mRNA and expression of protein in vivo. Furthermore, FDCs up-regulated both RGS13 and RGS16 mRNA expression in non-GC T cells, resulting in their impaired migration to CXCL12. Finally, GC T cells down-regulated RGS13 and RGS16 expression in the absence of FDCs and regained migratory competence to CXCL12. Although GC T cells express high levels of CXCR4, signaling through this receptor appears to be specifically inhibited by FDC-mediated expression of RGS13 and RGS16. Thus, FDCs appear to directly affect GC T cell migration within lymphoid follicles.

Original languageEnglish (US)
Pages (from-to)6169-6178
Number of pages10
JournalJournal of Immunology
Volume173
Issue number10
DOIs
StatePublished - Nov 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Estes, J. D., Thacker, T. C., Hampton, D. L., Kell, S. A., Keele, B. F., Palenske, E. A., Druey, K. M., & Burton, G. F. (2004). Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration. Journal of Immunology, 173(10), 6169-6178. https://doi.org/10.4049/jimmunol.173.10.6169