thymocytes

Thymocytes are developing T lymphocytes that reside in the thymus during their maturation. They originate from hematopoietic stem cells that migrate from the bone marrow and enter the thymus, where they undergo a program of rearrangement and selection to become mature T cells. Early thymocytes lack CD4 and CD8 expression (double-negative) and pass through stages defined by surface markers and T-cell receptor gene rearrangements.

During the double-negative stages, thymocytes rearrange the TCR beta chain and undergo a checkpoint known as beta selection, which requires a functional pre-TCR to promote proliferation and progression to the double-positive stage. The majority then express both CD4 and CD8 (double-positive). At this stage, the alpha chain is rearranged to form a complete TCR, enabling antigen recognition in the context of self MHC molecules.

Positive and negative selection occur as thymocytes interact with the thymic microenvironments. Positive selection in the cortex favors thymocytes that bind self MHC-peptide with appropriate affinity, leading to survival and lineage commitment to either CD4 or CD8 single-positive cells. Negative selection, primarily in the medulla, removes thymocytes with high affinity for self-antigens. Medullary thymic epithelial cells, aided by dendritic cells and macrophages, express a broad array of tissue-restricted antigens (Aire-dependent) to promote central tolerance and prevent autoimmunity.

Mature thymocytes exit the thymus with a naive T-cell phenotype, typically CD4+ or CD8+, ready to populate peripheral lymphoid organs. Thymocyte development is regulated by signals such as Notch1, interleukin-7, and the TCR/CD3 complex, which collectively coordinate survival, proliferation, and lineage decisions.