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

Regulatory T cells (Tregs) and beta-galactoside-binding protein (beta GBP), 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 beta GBP to control CD8(+) T cell responses partially activating TCR signaling but blocking PI3K activity. As a result, this leads to a loss of p21(ras), ERK and Akt activities despite activation of TCR proximal signals, such as phosphorylation of CD3 zeta, Zap70, Lat and PKC theta. Although non-processive TCR signaling often leads to cell anergy, Tregs/beta GBP did not affect cell viability. Instead, beta GBP/Tregs transiently prevented activation of CD8(+) T cells with self-antigens, while keeping their responses to xenogeneic antigens unaffected. Published by Elsevier Inc.