Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals

Linhua Zou, Brian Barnett, Hana Safah, Vincent F. LaRussa, Melina Evdemon-Hogan, Peter Mottram, Shuang Wei, Odile David, Tyler J. Curiel, Weiping Zou

Research output: Contribution to journalArticle

285 Scopus citations

Abstract

CD4+CD25+ regulatory T cells (Tregs) mediate peripheral T-cell homeostasis and contribute to self-tolerance. Their homeostatic and pathologic trafficking is poorly understood. Under homeostatic conditions, we show a relatively high prevalence of functional Tregs in human bone marrow. Bone marrow strongly expresses functional stromal-derived factor (CXCL12), the ligand for CXCR4. Human Tregs traffic to and are retained in bone marrow through CXCR4/CXCL12 signals as shown in chimeric nonobese diabetic/severe combined immunodeficient mice. Granulocyte colony-stimulating factor (G-CSF) reduces human bone marrow CXCL12 expression in vivo, associated with mobilization of marrow Tregs to peripheral blood in human volunteers. These findings show a mechanism for homeostatic Treg trafficking and indicate that bone marrow is a significant reservoir for Tregs. These data also suggest a novel mechanism explaining reduced acute graft-versus-host disease and improvement in autoimmune diseases following G-CSF treatment.

Original languageEnglish (US)
Pages (from-to)8451-8455
Number of pages5
JournalCancer Research
Volume64
Issue number22
DOIs
StatePublished - Nov 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zou, L., Barnett, B., Safah, H., LaRussa, V. F., Evdemon-Hogan, M., Mottram, P., Wei, S., David, O., Curiel, T. J., & Zou, W. (2004). Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Research, 64(22), 8451-8455. https://doi.org/10.1158/0008-5472.CAN-04-1987