Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice

Zachary S. Buchwald, Jennifer R. Kiesel, Chang Yang, Richard DiPaolo, Deborah V. Novack, Rajeev Aurora

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23 Scopus citations


Osteoimmunology is the crosstalk between the skeletal and immune systems. We have previously shown in vitro that osteoclasts (OC) crosspresent antigens to induce FoxP3 in CD8 T-cells (OC-iTcREG), which then suppress osteoclast activity. Here we assessed the ability of OC-iTcREG to limit bone resorption in vivo. Mice lacking CD8 T-cells lose more bone in response to RANKL (Tnfsf11) administration. Using adoptive transfer experiments we demonstrate that FoxP3+ CD8 T-cells limit bone loss by RANKL administration. In ovariectomized mice, a murine model of postmenopausal osteoporosis, OC-iTcREG limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTcREG-treated ovariectomized mice had decreased levels of effector T-cells in the bone marrow compared to untreated mice, and increased bone formation rates relative to bisphosphonate-treated mice. Our results provide the first in vivo evidence that OC-iTcREG have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
Issue number1
StatePublished - Sep 1 2013


  • FoxP3 CD8 T-cells
  • Negative feedback
  • Osteoclasts
  • Osteoimmunology
  • Osteoporosis

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    Buchwald, Z. S., Kiesel, J. R., Yang, C., DiPaolo, R., Novack, D. V., & Aurora, R. (2013). Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice. Bone, 56(1), 163-173. https://doi.org/10.1016/j.bone.2013.05.024