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Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro.
- Source :
- PLoS ONE; Jun2012, Vol. 7 Issue 6, p1-12, 12p
- Publication Year :
- 2012
-
Abstract
- Background: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T<subscript>EFF</subscript>) increase bone resorption by osteoclasts. Prolonged exposure to the T<subscript>EFF</subscript> produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc<subscript>REG</subscript>). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. Principal Findings: To determine the net effect of Tc<subscript>REG</subscript> on osteoclast activity we used a number of in vitro assays. We found that Tc<subscript>REG</subscript> can potently and directly suppress bone resorption by osteoclasts. Tc<subscript>REG</subscript> could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc<subscript>REG</subscript> suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc<subscript>REG</subscript> by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc<subscript>REG</subscript> does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc<subscript>REG</subscript> and osteoclasts. Significance: We have determined that osteoclast-induced Tc<subscript>REG</subscript> can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology. [ABSTRACT FROM AUTHOR]
- Subjects :
- OSTEOCLASTS
BONE cells
T cells
CYTOKINES
CELLULAR immunity
BONE resorption
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 79825589
- Full Text :
- https://doi.org/10.1371/journal.pone.0038199