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[Cancer Research 64, 8451-8455, November 15, 2004]
© 2004 American Association for Cancer Research

Immunology

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 and Weiping Zou

Tulane University Health Science Center, Section of Hematology and Medical Oncology, New Orleans, Louisiana

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.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2004 by the American Association for Cancer Research.