Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals.
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.
Zou
Linhua
L
Tulane University Health Science Center, Section of Hematology and Medical Oncology, New Orleans, Louisiana 70112-2699, USA.
Barnett
Brian
B
Safah
Hana
H
Larussa
Vincent F
VF
Evdemon-Hogan
Melina
M
Mottram
Peter
P
Wei
Shuang
S
David
Odile
O
Curiel
Tyler J
TJ
Zou
Weiping
W
D001483:Base Sequence; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D017931:DNA Primers; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017931:DNA Primers; D019718:Receptors, CXCR4; D015375:Receptors, Interleukin-2; D016179:Granulocyte Colony-Stimulating Factor