Mimicking The Thymus - A Tool In The Battle Against HIV

December 03, 1997

The thymus, the small organ located just above the heart, is the site of development of the class of white blood cells called T cells. T cells develop from primitive precursor cells called stem cells, which migrate to the thymus from the bone marrow. This thymic development is known as T-lymphopoiesis. The structure and function of the thymus is impaired in babies infected with the Human Immunodeficiency Virus (HIV). Now for the first time, British scientists have developed a system which allows them to mimic the thymus in a test tube and study T-lymphopoiesis with greater ease. At the British Society for Immunology Annual Congress in Brighton this week Dr Andrew Freedman of the University of Wales College of Medicine, Cardiff will describe the system and explain how they are using it to offer hope to HIV positive children and adults.

There have been previous attempts to recreate T-lymphopoiesis in the laboratory, for example using humanised mice grafted with human thymic tissue. However, such techniques are very difficult to perform and it is also difficult to isolate the T cells at different stages of their development.

Dr. Freedman and his colleagues have shown that a much less sophisticated system is needed to promote T cell development than previously thought and have produced a system analogous to that already successfully used for long-term bone marrow culture.

A suspension of foetal thymus cells is grown in tissue culture for about two weeks until a single layer of cells is formed. Stem cells are obtained from bone marrow or umbilical cord blood and placed on top of the layer of thymic cells. Some immune system messenger molecules, called cytokines, are added and then all the researchers have to do is sit back and wait - the stem cells develop into fully mature T cells over a period of 4-6 weeks.

As well as studying what happens during normal T cell development, the Welsh researchers are also using their new model to look at the effect of HIV infection on the process, important since T cells are the cells primarily infected by the virus. The thymus is most important to us as babies and young children - after adolescence the thymus gradually shrinks. Therefore any disruption caused by HIV infection will have most effect on the young. Using their thymus model, the team has shown that even immature T cells are susceptible to infection by HIV. The team is now investigating the effects of HIV on the thymic cells themselves to see whether infection of these cells is the cause of the thymic dysfunction seen in HIV.

Another important application of the system is in the evaluation of gene therapy targeted at T cells. Dr Freedman and his colleagues have shown that if a marker gene is placed inside a stem cell before being cultured in the thymus mimic, the gene continues to work as the cell develops. Stem cell gene therapy has been suggested as a potential treatment for people with advanced HIV infection and this new system would play a vital role in testing such a therapy prior to clinical trials.

Notes:


1. Dr Freedman is speaking in the Lymphopoeisis session on Wednesday 3 December. The BSI 5th Annual Congress is at the Brighton Centre from 2-5 December 1997.


2. Dr Freedman can be contacted at Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN Tel: +44 1 222 743 405


3. There will be a press office at the meeting in operation from 9am on Tuesday 2 December, tel: +44 1 273 724 320 / 0378 406 416. Journalists are welcome to attend but are requested to contact Kirstie Urquhart in advance to register.


4. Before the meeting Kirstie can be contacted on +44 181 875 2402 /
kirstie@immunology.org

British Society For Immunology

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