The immune system plays a pivotal role during bone remodeling process. Orthodontic tooth movement (OTM) induces local inflammation in periodontium, but whether systemic immune response is involved in OTM remains unknown. In this study, we show that tooth movement distance was significantly reduced in T-cell-deficient immunocompromised mice compared with wild-type (WT) mice. Intravenous infusion of allogeneic T cells to the immunocompromised mice rescued the OTM distance. Correspondingly, increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were detected around the alveolar bone after OTM in WT mice but were barely detected in immunocompromised mice. Moreover, intravenous infusion of T cells rescued the number of TRAP-positive osteoclasts in the OTM area of the immunocompromised mice, thus suggesting T cells are required for OTM. We then reveal that OTM induced a significant elevation of type 1 T helper cell (Th1) cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) around periodontal tissue in WT but not in immunocompromised mice. Infusion of T cells could increase the levels of TNF-alpha and IFN-gamma in periodontal tissues of immunocompromised mice. More interestingly, intraperitoneal injection of TNF-alpha inhibitor etanercept significantly reduced the distance of OTM in T-cell-infused immunocompromised mice. In summary, this study demonstrates a previously unrecognized mechanism that T cells are required for OTM depending on Th1-associated cytokines.
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