Bone Marrow Is a Reservoir for CD4+CD25+ Regulatory T Cells that Traffic through CXCL12/CXCR4 Signals

L Zou, B Barnett, H Safah, VF LaRussa… - Cancer research, 2004 - AACR
L Zou, B Barnett, H Safah, VF LaRussa, M Evdemon-Hogan, P Mottram, S Wei, O David…
Cancer research, 2004AACR
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 …
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.
AACR