The thymus trains your immune cells, then quietly turns to fat
Behind the breastbone sits an organ that is biggest in childhood and fades after puberty. The thymus is a boot camp for T cells: most recruits are culled, either for failing to recognise the body's signalling molecules or for attacking its own tissues. Its role only became clear in the 1960s.
The organ has two lobes resting on the membrane around the heart, reaching from below the thyroid down as far as the fourth rib. Each lobe has a dense outer cortex packed with immature T cells, called thymocytes, and a paler inner medulla. At birth it measures roughly 4 to 6 centimetres long. It grows to around 20 to 50 grams by puberty and later shrinks to perhaps 5 to 15 grams, sometimes becoming hard to spot at all. The Ancient Greeks knew it existed, but its immune job stayed obscure until the 1960s.
Precursor cells arrive from the bone marrow and shuffle gene segments to build a unique receptor. That shuffling is error-prone, so selection follows. In the cortex, cells whose receptors fail to bind MHC molecules, the proteins that display fragments for inspection, die off. In the medulla, cells that react strongly to the body's own proteins are eliminated; a gene called AIRE makes medullary cells display proteins from all over the body so rogue T cells can be caught. A few self-reactive cells are spared and become regulatory T cells.
Shrinkage, known as involution, is driven by rising sex hormones; experiments show castration makes the adult thymus grow again. Fat cells invade after puberty, working in from the partitions between lobules. The pattern appears in most or all vertebrates with a thymus, pointing to an ancient, conserved process. Mouse studies suggest an older thymus selects a less varied set of T cell receptors, with its supporting tissue driving much of the change.
When the thymus fails to form, the consequences are severe. DiGeorge syndrome, caused by a deletion on chromosome 22, is the commonest inborn cause and can be treated with thymus transplantation. Laboratory nude mice, which lack both hair and a thymus because of a FOXN1 mutation, serve as a standard research model of T cell deficiency.
Source: Thymus
