Activation status of ?? T cells dictates their effect on osteoclast generation and bone resorption.
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ABSTRACT: ?? T cells, a small subset of T cell population (5-10%), forms a bridge between innate and adaptive immunity. Although the role of ?? T cells in infectious diseases and antitumor immunity is well investigated, their role in bone biology needs to be explored. Aminobisphosphonates are used as a standard treatment modality for bone related disorders and are potent activators of ?? T cells. In the present study, we have compared the effect of "activated" and "freshly isolated" ?? T cells on osteoclast generation and function. We have shown that "activated" (?CD3/CD28 + rhIL2 or BrHPP + rhIL2 stimulated) ?? T cells inhibit osteoclastogenesis, while "freshly isolated" ?? T cells enhance osteoclast generation and function. Upon stimulation with phosphoantigen (BrHPP), "freshly isolated" ?? T cells were also able to suppress osteoclast generation and function. Cytokine profiles of these cells revealed that, "freshly isolated" ?? T cells secrete higher amounts of IL6 (pro-osteoclastogenic), while "activated" ?? T cells secrete high IFN? levels (anti-osteoclastogenic). Neutralization of IFN? and IL6 reversed the "inhibitory" or "stimulatory" effect of ?? T cells on osteoclastogenesis. In conclusion, we have shown that, activation status and dynamics of IL6 and IFN? secretion dictate pro and anti-osteoclastogenic role of ?? T cells.
SUBMITTER: Phalke SP
PROVIDER: S-EPMC5365245 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
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