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Liver sinusoidal endothelial cells: a new type of organ-resident antigen-presenting cell

100%

Limmer A., Knolle P. A.

Archivum Immunologiae et Therapiae Experimentalis

2001

vol. 49

issue 1 suppl.

7-12

The induction of peripheral immune tolerance in the liver is a well-known phenomenon that is operative in different situations such as tolerance to organ transplants and tolerance to oral antigens. The mechanisms leading to peripheral immune tolerance in the liver are still incompletely understood. While different cell populations of the liver have been implicated in and probably contribute in concert to the induction of hepatic immune tolerance, one hepatic cell type in particular seems to be suited for tolerance induction: liver sinusoidal endothelial cell (LSEC). LSEC are microvascular endothelial cells with a unique phenotype reminiscent of dendritic cells and a unique function as antigen-presenting cells for CD4+ T cells. The hepatic microenvironment, i.e. portal venous constituents and soluble mediators from sinusoidal cell populations, tightly control antigen presentation by LSEC to avoid immune-mediated damage. LSEC, in contrast to other endothelial cells, have the capacity to prime naive CD4+ T cells and induce cytokine release. Importantly, naive CD4+ T cells primed by antigen- presenting LSEC differentiate into regulatory T cells whereas T cells primed by bone marrow-derived professional antigen presenting cells differentiate into Th1 cells. Thus, LSEC represent a new type of organ resident ?non-professional? antigen-presenting cell that appears to be involved in the local control of the immune response and the induction of immune tolerance in the liver.

Treating autoimmune diseases through restoration of antigen-specific immune tolerance

75%

Wolfraim L. A.

Archivum Immunologiae et Therapiae Experimentalis

2006

vol. 54

issue 1

1-13

The first line of treatment for many human autoimmune diseases involves the use of anti-inflammatory or immunosuppressive drugs such as prednisone or other steroids that not only suppress the underlying autoimmune disease, but lead to global suppression of the immune system. The sequelae of this approach include increased risk of infection, carcinogenesis, and osteoporosis. Moreover, such broad spectrum immunosuppression tends to have transient therapeutic benefit, as in many cases the disease becomes refractory to these drugs. There is a clear need for more specific means to restore immune tolerance to the specific autoantigens implicated in disease pathology. This review provides an overview of some of these newer, more specific therapeutic approaches to restoring immune tolerance to autoantigens, with an emphasis on those approaches that have been or will soon be tested in controlled clinical trials. Covered here are peptide- or protein-based therapeutics, oral tolerance, and cellular and gene therapy approaches to restoring antigen-specific immune tolerance.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2006

1 2001

1 Knolle P. A.

1 Limmer A.

1 Wolfraim L. A.

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Liver sinusoidal endothelial cells: a new type of organ-resident antigen-presenting cell

Treating autoimmune diseases through restoration of antigen-specific immune tolerance