T cell-dependent regulatory roles of 18-kDa Translocator protein (TSPO)

Abstract

Abstract Objective: TSPO (also called PBR) is a translocator protein that is localized on the outer mitochondrial membrane. TSPO is broadly and constitutively expressed in various types of immune cells including macrophages, monocytes, T cells, and B cells. Although many studies have shown that TSPO negatively regulates innate immune cell, such as macrophage and monocyte, activity, the roles of TSPO in T cell-mediated immune responses remain unclear. In this study, we examine the effects of Ro5-4864, a TSPO agonistic ligand, in an DNFB-induced contact hypersensitivity murine model. Results and Discussion: TSPO expression in draining lymph nodes (dLNs) was elevated after sensitization. Ro5-4864 treatment at sensitization, but not at challenge, significantly suppressed ear swelling. The total cell numbers in the dLNCs were decreased by Ro5-4864 treatment. In the Ro5-4864-treated mice, the ratios of IFN-γ expressing CD4+ T cells and CD8+ T cells in dLNs were decreased. Adoptive transfer of Ro5-4864-treated sensitized T cells into naive mice inhibited ear swelling after ear challenge. Ro5-4864-treated sensitized T cells showed lower proliferative responses against DNFB-pulsed antigen presenting cells. Our results demonstrated that treatment with Ro5-4864 inhibited DNFB-induced contact hypersensitivity, suggesting the regulatory roles of TSPO in T cell-depending immune responses.