Thymus: T lymphocyte maturation and central tolerance

The thymus is a small organ in the upper chest, behind the breastbone. It lies in the superior mediastinum (the central compartment of the chest) and is most active in early life. After puberty it shrinks and is replaced by fat.

It is a primary lymphoid organ, which means T lymphocytes mature there rather than responding to infection. Immature T cells arrive from the bone marrow, and each one builds its own receptor by random rearrangement of genes. This inevitably produces some receptors that recognise the body's own proteins, so the cells have to be tested.

Each developing T cell has to pass two checks. In positive selection, in the cortex (outer part), cells whose receptors can recognise the body's own MHC molecules are kept. MHC molecules are the display proteins that show antigen fragments to T cells, and cells that cannot recognise them die. In negative selection, in the medulla (inner part), cells that bind too strongly to the body's own antigens receive a death signal and are removed.

Destroying these self-reactive cells (cells that react strongly to the body's own antigens) where T cells are made is called central tolerance. Only a minority of developing T cells survive. The survivors leave as naive T cells, which have yet to meet their antigen, and travel in the blood to lymph nodes, the spleen and other tissues to wait for it.

Central tolerance helps to prevent autoimmune disease, in which the immune system attacks the body's own tissues, but it is imperfect. Some self-reactive cells escape. In myasthenia gravis the immune system makes antibodies against the acetylcholine receptor at the neuromuscular junction (the joint between nerve and muscle), which causes fluctuating muscle weakness, and the thymus is sometimes abnormal, which suggests that tolerance may be failing.