Thymocyte

Thymocytes are immature T lymphocytes that develop in the thymus. They originate from hematopoietic stem cells in the bone marrow and migrate to the thymus to undergo maturation, selection, and rearrangement of their T cell receptor genes before entering the circulation as mature T cells.

During development thymocytes progress through defined stages. The earliest thymocytes are double-negative (DN), lacking CD4 and CD8 expression, and can be subdivided (DN1 to DN4) by markers such as CD44 and CD25. In these cells, T cell receptor beta (TCRβ) genes undergo rearrangement, leading to a pre-TCR signal that promotes survival and proliferation. Cells then become double-positive (DP), expressing both CD4 and CD8, and rearrange the TCR alpha chain to form a complete αβ T cell receptor with CD3.

Selection processes shape the T cell repertoire. Positive selection in the thymic cortex tests DP thymocytes for relatively low-affinity recognition of self-MHC presenting self-peptides; only thymocytes whose TCRs can interact with self-MHC survive. Negative selection in the medulla eliminates thymocytes with high-affinity reactivity to self-antigens, aided by medullary thymic epithelial cells and dendritic cells, and often resulting in clonal deletion or development into regulatory phenotypes. AIRE drives ectopic expression of tissue-restricted antigens to promote tolerance.

Surviving thymocytes exit the thymus as mature, naive T cells—CD4+ or CD8+ single-positive cells—that populate peripheral lymphoid organs. The thymic process, including selection and tolerance, is central to preventing autoimmunity and shaping the diversity of the adaptive immune response.