The immunological microenvironment in the synovium during experimental polyarthritis in the rat [ 2003 - 2005 ]

Research Grant

Researchers: A/Pr Graham Mayrhofer (Principal investigator) ,  Prof Leslie Cleland

Brief description In this project, we aim to understand the process by which some forms of arthritis, as exemplified by rheumatoid arthritis (RA), cause inflammation and destruction of multiple joints. Such forms of arthritis are referred to collectively as polyarthritis. There is a strong evidence that RA has an immunological basis and that abnormal recognition of components of the joints by T lymphocytes orchestrates the inflammation that is characteristic of the disease. We believe that dispersal of disease-causing activated T lymphocytes in the blood accounts for the involvement of many joints. We have used a model of polyarthritis in rats to study the nature of the activated T lymphocytes, where they come from, how they are delivered to the blood stream and how they enter the joints. This project focuses on the crucial tissues that line the joints. We want to understand how the disease-causing activated T cells cause inflammation and how the immune system reacts to restrain them. We can undertake this work because we have developed three unique tools. Firstly, we can transfer arthritis with activated T lymphocytes and, therefore, study their behavior in an otherwise normal body. In this way, we can see how the body responds to the presence of disease causing cells. Secondly, we have introduced a genetic marker, which is essential if one wishes to distinguish the separate activities of the donor' and host cells. Thirdly, we can collect cells from the diseased paws, allowing us to examine their activities in vitro as well as in vivo. This model offers the opportunity to study the activities of the disease-causing cells and to identify points at which the disease cycle can be broken. It will allow us to design and-or test new treatments aimed at these points.

Funding Amount $AUD 473,250.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant