Functional Genomic Analysis of NK and NKT Cell Immune Control of Autoimmunity

Funded Activity Summary

The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reason why autoimmunity occurs is thought to be due to a failure in the mechanisms responsible for controlling such unwanted responses. Two other populations of white blood cells are involved in this regulation, termed NK and NKT cells, each of which release important cell hormones. The current project is designed to test whether defects in NK and NKT cells lead to autoimmune disease. For this purpose a special strain of mice (NOD mice) will be used. The reasons for their selection are: 1) they are highly susceptible to a range of autoimmune diseases including diabetes, lupus and anaemia, and 2) we and others have found that they are deficient in both NK and NKT cells. The proposed experiments are divided into two groups, one designed to characterise the nature of the defects in these cells and the other to identify the genes responsible for them. In this way it should be possible to shed light on the genetic basis of autoimmune diseases in general. The approach to be used involves sophisticated techniques of genetic analysis, which require production of special congenic lines of mice. These mice are like NOD mice but carry in addition to NOD genes genetic regions from a non-autoimmune strain with the potential to correct the defects in NK and NKT cells. In this way, it should be possible to pinpoint the disease susceptibility genes involved in causation of autoimmunity and to work out how they affect NK and NKT cells.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $692,040.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Emergency medicine

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Congenic and transgenic mice | Hemolytic anaemia | Immune regulation | Immunogenetics | NK cells | NKT cells | Systemic lupus erythematosus | Type 1 diabetes

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