Tregs utilize β-galactoside-binding protein to transiently inhibit PI3K/p21ras activity of human CD8+ T cells to block their TCR-mediated ERK activity and proliferation

Abstract: Regulatory T cells (Tregs) and beta-galactoside-binding protein (βGBP), a regulatory protein often found expressed at sites of immunological privilege, have similar functions. Their presence affects the outcome of harmful autoimmunity and cancers, including experimental autoimmune encephalomyelitis and malignant gliomas. Here we report a novel pathway by which Tregs express and utilize βGBP to control CD8+ T cell responses partially activating TCR signaling but blocking PI3K activity. As a result, this leads to a loss of p21ras, ERK and Akt activities despite activation of TCR proximal signals, such as phosphorylation of CD3ζ, Zap70, Lat and PKCθ. Although non-processive TCR signaling often leads to cell anergy, Tregs/βGBP did not affect cell viability. Instead, βGBP/Tregs transiently prevented activation of CD8+ T cells with self-antigens, while keeping their responses to xenogeneic antigens unaffected. [Copyright &y& Elsevier]