Regulatory T Cells in the Mosaic of Liver Transplantation Tolerance

The success of transplantation depends on multiple factors, but the establishment of immune tolerant milieu is of critical importance. Hepatic environment consists of different cellular populations with prominent capacity to tolerate a huge range of antigens. Among them, regulatory T cells (Tregs) play an important role. They control the strength of immune reactions against non-self antigens and were shown to have an impact on the establishment of immune tolerance in the post-transplantation period. Furthermore, they impact a particular state after transplantation – operational tolerance. The abundant data show that Tregs might be manipulated, which suggests their further implementation as a treatment strategy. Tregs are also a very attractive target as a biomarker in the monitoring of post-transplantation period. Here, we review the particular role of Tregs among the broad spectrum of immune tolerance mechanisms of the liver in the light of the current directions of medical research.

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Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells

European Journal of Immunology ◽

10.1002/eji.1830241019 ◽

1994 ◽

Vol 24 (10) ◽

pp. 2383-2392 ◽

Cited By ~ 131

Author(s):

Ralph Scully ◽

Shixin Qin ◽

Stephen Cobbold ◽

Herman Waldmann

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Transplantation Tolerance ◽

Kinetics Of

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Antigen in the Absence of DAMPs Promotes Immune Tolerance: The Role of Dendritic Cells and Regulatory T Cells

Damage-Associated Molecular Patterns in Human Diseases ◽

10.1007/978-3-319-78655-1_33 ◽

2018 ◽

pp. 791-827

Author(s):

Walter Gottlieb Land

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Immune Tolerance

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Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

Clinical and Developmental Immunology ◽

10.1155/2013/617595 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Mark Engel ◽

Tom Sidwell ◽

Ajithkumar Vasanthakumar ◽

George Grigoriadis ◽

Ashish Banerjee

Keyword(s):

T Cells ◽

Transcription Factors ◽

T Cell ◽

Regulatory T Cells ◽

Immune Tolerance ◽

Regulatory T Cell ◽

T Cell Development ◽

Signalling Pathways ◽

Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

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Regulatory T Cells in Hepatic Immune Tolerance and Autoimmune Liver Diseases

Digestive Diseases ◽

10.1159/000440750 ◽

2015 ◽

Vol 33 (Suppl. 2) ◽

pp. 70-74 ◽

Cited By ~ 8

Author(s):

Johannes Herkel

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Immune Tolerance ◽

Liver Diseases ◽

Liver Sinusoidal Endothelial Cells ◽

Autoimmune Liver Diseases ◽

Specific Control

Regulatory T cells (Tregs) have a profound ability to control immune responses. A majority of Tregs are derived from the thymus; yet a substantial Treg fraction is derived from the periphery. The liver seems to be an important source of peripherally derived Tregs. Indeed, the liver's well-known ability to induce immune tolerance is at least partly based on hepatic Treg generation. With recently developed tools to deliver antigens to tolerance-inducing liver cells, it is now possible to harness liver-derived Tregs for specific control of unwanted immune responses. Indeed, the selective delivery of autoantigens to liver sinusoidal endothelial cells could induce autoantigen-specific Tregs in vivo, providing effective treatment of autoimmune disease. Owing to the fundamental role Tregs play in controlling immune responses, an impairment of Tregs seems to be a plausible explanation for the development of autoimmune diseases, for example, in the liver. However, the actual role of Treg impairment in autoimmune liver diseases, such as autoimmune hepatitis (AIH), remains controversial. Major obstacles for clarifying the role of Tregs in autoimmune liver diseases are related to the difficulty to identify human Tregs unambiguously and to the difficulty to identify those Tregs and effector T cells that specifically recognize disease-driving autoantigens. However, even if AIH turned out to be a disease that is not driven by Treg impairment, Treg-based therapies for autoimmune liver diseases might still be effective, provided the Tregs for therapeutic use recognize the relevant antigens.

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