Abstracts (complete list) - Wissenschaft Online

Gamze Kabalak, Torsten Matthias, Reinhold E. Schmidt, Torsten Witte
FUNCTIONAL CHARACTERISATION OF ILT6 AS GENETIC RISK
FACTOR FOR MULTIPLE SCLEROSOS AND SJÖGREN’S
SYNDROME
Introduction: Autoimmune diseases Multiple Sclerosis (MS) and Sjögren’s syndrome
(SS) are polygenic disorders and appear to be triggered by EBV infection. Risk genes for
Multiple sclerosis (MS) are localized on chromosome 6 and the chromosomal region
19q13.4, the later harboring the genes of the Immunoglobulin-like transcripts (ILTs).
ILTs are expressed on antigen presenting cells, T and NK cells and play a role in the
tolerance induction of the immune system by interacting with regulatory T cells. A
homozygous deficiency of ILT6 was shown to be associated with MS and SS. As ILT6 is
lacking a transmembrane domain, it is likely to be secreted and may act as a soluble
mediator. To address the question of the role of ILT6 the recombinant protein was
expressed and functional studies were performed.
Methods: Adhesion tests with MCF-7 cells and ILT6 were performed. These cells express
MHC class I on there surface. Therefore T cell clones expressing either CD8 alpha or
beta were incubated together with MCF-7 cells in the presence or absence of ILT6.
Further mixed lymphocyte reaction (MLR) as well as cytotoxicity assays were performed
with changing concentrations of ILT6.
Results: These experiments revealed a concentration dependent blockade of the
interaction of CD8 α and MHC I by ILT6. Furthermore the proliferation of T cells in the
MLR was increased by addition of ILT6. On the other hand cytotoxicity assays showed
no influence of ILT6 on NK cells.
Conclusion: ILT6 may act as a natural immunomodulator with profound effect on T cells.
Supported by Gemeinnuetzige Hertie Stiftung, Sicca-Forschungsfoerderung and BMBF
KN Rheuma C2.12