Possible Involvement of γδ T Cells in Osteoclastogenesis

Objectives: Osteoimmunological response that is mediated by interplay between bone cells and lymphocytes plays a role in bone remodeling in oral craniofacial area. It is reported that subsets of αβ T cell receptor (TCR) T cells, such as, Th17, Th1 or Treg, affect bone remodeling by the production of osteoclastogenesis (OCgenesis) up- or down-regulatory factors, RANKL, IFN-γ or IL-10, respectively. On the other hand, possible enrolment of γδ TCR T cells which consist only 1-5% of whole T cell population in bone remodeling process remains unclear. The present study investigated the possible regulatory roles of γδ T cells in the OCgenesis.
Methods: Adult γδ TCR knockout (γδ KO) mice (12-w, female) and age/sex-matched wild type (WT) mice (C57BL/6J) were used.
Results: γδ KO mice demonstrated significantly lower bone mineral density (BMD) in femur than WT mice. In response to in vitro stimulation with RANKL and M-CSF, mononuclear cells isolated from bone marrow (BM) of γδ KO mice developed significantly more TRAP positive multinucleated cells than WT-BM cells. Furthermore, the number of nuclei per TRAP positive cell was significantly higher in γδ KO-BM than WT-BM cells, indicating that cell-cell fusion process may be suppressed by the presence of γδ T cells. Only IFN-γ concentration was significantly higher in WT-BM cell culture than γδ KO-BM suggesting that IFN-γ, a known OCgenesis-inhibitor, appears to be responsible for down-regulation of OCgenesis mediated by γδ T cells. Regarding the effect of γδ T cells on bone remodeling in vivo, the transfer of WT γδ T cells to γδ KO mice restored its BMD at the same level of control WT mice. However, the γδ KO mice that received γδ T cells from IFN-γ KO did not show any statistically significant change of BMD.
Conclusions: These findings suggest that γδ T cells may play a regulatory role in RANKL-induced OCgenesis.