CD4+T cell specific B7-H1 selectively inhibits proliferation of naïve T cells and Th17 differentiation in experimental autoimmune encephalomyelitis

Abstract

It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4+T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice. We also found the proliferation of naïve CD4+CD62+T cells isolated from B7-H1 transgenic mice was inhibited. And naïve T cells isolated from B7-H1 transgenic mice produced fewer Th17 cells than WT mice in Th17-polarizing conditions, but the Th1, Th2, and inducible Treg differentiation were the similar in naïve T cells isolated from B7-H1 transgenic mice and WT mice. In conclusion, our study show CD4+T cells specific B7-H1 is a slective inhibitor in proliferation of naïve T cells, Th17 differentiation and pathogenesis of multiple sclerosis.

Expression and clinical significance of negative costimulatory molecules B7-H1, B7-H3 and B7-H4 in the process of colorectal cancer’s evolution

“…These costimulatory signaling molecules provide positive signals for T cell growth, differentiation, and cytokine production. They also limit, weaken, or terminate T cell immune responses by providing negative signals and mediating immune escape by a variety of mechanisms that allow tumor cells to escape an immune attack (5). The current study suggests that B7-H1, B7-H3, B7-H4 which are negative costimulatory molecules belong to the B7 family.…”

Monocytes show immunoregulatory capacity on CD4+ T cells in a humanin-vitromodel of extracorporeal photopheresis

“…To further investigate the reduction of T cell proliferation by ECP‐treated monocytes, we examined possible check‐points of immunomodulation. PD‐L1 is known to suppress T cell activity and to reduce tumour cell killing via binding of its receptor PD‐1 . PD‐L1–PD‐1 interactions further lead to a cell cycle arrest in the G 0 /G 1 phase, whereas binding of PD‐L2 to PD‐1 leads to the inhibition of T cell receptor‐mediated proliferation .…”

“…PD‐L1–PD‐1 interactions further lead to a cell cycle arrest in the G 0 /G 1 phase, whereas binding of PD‐L2 to PD‐1 leads to the inhibition of T cell receptor‐mediated proliferation . Indeed, PD‐L1 is not only described to be an inhibitor for T cell proliferation but also for Th17 differentiation , and PD‐L1 signalling was assigned to play an important role in down‐regulation of immune responses in an ECP model of iDCs and ECP‐treated responder cells.…”