| Summary: | Binding Immunoglobulin Protein (BiP) is a member of the HSP70 family and is currently being used in clinical trials to treat rheumatoid arthritis. Soluble BiP has been shown to have immunoregulatory properties in murine models of arthritis and human immune cells in vitro. Regulatory T cells are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease. Published data suggest that HSP60 and HSP70 can enhance regulatory T cell function, and therefore the ability of soluble BiP ability to affect regulatory T cell frequency and function was examined. Using the Whitehall II cohort, the concentration of soluble BiP does not correlate with regulatory T cell frequencies. Two hours of BiP pre-treatment did not enhance regulatory T cell function as demonstrated in in vitro suppression assays. However, treatment of responder T cells with BiP for 4 days following stimulation with anti-CD3/CD28 beads or indirectly following co-culture with monocytes treated with BiP reduced their proliferation. Since the BiP effect on responder T cells can be observed after 4 days in culture, regulatory T cells were cultured with BiP for 4 days. BiP pre-treatment for 4 days of regulatory T cells had no effect on the phenotype, cytokine secretion and function of regulatory T cells. Then, the effect of BiP on responder T cells was investigated. Responder T cells cultured with BiP revealed a significant increase in Foxp3+CD25+ cells and IL-10 secretion within the responder T cell population cultured with BiP. The BiP-induced CD25HighFoxp3+ T cell ability to suppress responder T cells were variable but these cells can reduce TNF-α secretion from autologous responder T cells in the co-culture. In conclusion, BiP may modulate responder T cell phenotype and function.
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