T Cell Education in the Thymus

Intrathymic T Cell Differentiation by Wilson Savino

T cells mature in the thymus after being tested for tolerance induction (negative selection) and MHC restriction (positive selection). This ensures that T cells (and B cells) do not recognize self antigens as dangerous, and that T cells recognize only antigens presented by self MHC.

Process of T cell education

1. Immature T cells from the bone marrow enter thymus via blood. T cells are "nude" and have no expression of Fas, CD4, CD8 or TCR. 
2. T cells migrate to the cortex, the outer region of the thymus, and proliferate. 
3. Some T cells start to encode α and β chains, and CD3 of the TCR complex. Later, they express both CD4 and CD8, and high levels of Fas, which receives apoptosis signals. 
4. MHC restriction: Using the Fas apoptotic scheme, cortical epithelial cells test positive selection for MHC recognition in T cells. (If MHC binding is too weak, then the T cell dies).
5. Central tolerance induction: T cells pass to the medulla (central thymus) and test tolerance for self using negative selection. Thymic DCs that have migrated from the bone marrow present self peptides to T cells. Medullary thymic epithelial cells also test tolerance for tissue-specific peptides. (If peptide binding is too strong, then the T cell dies). T cells are now single positive for either CD4 or CD8.