Zou Linhua, Barnett Brian, Safah Hana, Larussa Vincent F, Evdemon-Hogan Melina, Mottram Peter, Wei Shuang, David Odile, Curiel Tyler J, Zou Weiping
Tulane University Health Science Center, Section of Hematology and Medical Oncology, New Orleans, Louisiana 70112-2699, USA.
Cancer Res. 2004 Nov 15;64(22):8451-5. doi: 10.1158/0008-5472.CAN-04-1987.
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.
CD4(+)CD25(+)调节性T细胞（Tregs）介导外周T细胞稳态并有助于自身耐受。它们的稳态和病理迁移情况尚不清楚。在稳态条件下，我们发现人骨髓中功能性Tregs的比例相对较高。骨髓强烈表达功能性基质衍生因子（CXCL12），即CXCR4的配体。如在嵌合非肥胖糖尿病/重症联合免疫缺陷小鼠中所示，人Tregs通过CXCR4/CXCL12信号迁移至骨髓并保留在骨髓中。粒细胞集落刺激因子（G-CSF）在体内降低人骨髓CXCL12的表达，这与人类志愿者骨髓Tregs向外周血的动员有关。这些发现揭示了稳态Treg迁移的机制，并表明骨髓是Tregs的重要储存库。这些数据还提示了一种新机制，可解释G-CSF治疗后急性移植物抗宿主病减轻和自身免疫性疾病改善的原因。
