The role of the CD28-CD80 axis and molecular inhibitors of T cell co-stimulation in the potential treatment of autoimmune cholestatic liver diseases

Aliazis, Konstantinos ORCID: 0000-0003-1954-7914 (2022). The role of the CD28-CD80 axis and molecular inhibitors of T cell co-stimulation in the potential treatment of autoimmune cholestatic liver diseases. University of Birmingham. Ph.D.

Preview

Aliazis2022PhD.pdf
Text
Available under License All rights reserved.
Download (19MB) | Preview

Abstract

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by bile duct damage, increased portal inflammation and elevated inflammatory activity. In this work we studied the novel CD80 antagonist called RhuDex. Our aim was to block the CD28-CD80 pathway in vitro using liver-infiltrating mononuclear cells to study the effect of the drug in the liver of patients with PBC. RhuDex inhibited T cell proliferation in a co-stimulation system using autologous T cells co-cultured with transgenic CHO-CD80 cells. By phenotyping intrahepatic B cells, monocytes, and dendritic cells from patients with end-stage liver diseases we found that B cells and monocytes express the highest levels of CD80 and CD86, however no differences were detected across diseases. Co-culture of intrahepatic T cells with autologous B cells or monocytes in the presence of RhuDex inhibited T cell proliferation irrespective of the presence of CD80 on the surface of the antigen-presenting cells. Similar effects were seen in the absence of APC or upon strong T cell activation. These results demonstrate that RhuDex is a potent inhibitor with the capacity to modulate immune responses in the liver of PBC patients.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):