Maintaining CD4–CD8 lineage integrity in T cells: Where plasticity serves versatility

The divergence of the two αβ T cell subsets defined by the mutually exclusive expression of CD4 and CD8 glycoproteins is an important event during the intrathymic differentiation of T lymphocytes. This reviews briefly summarizes the mechanisms that promote commitment to the CD4 or CD8 lineage in the thymus, and discusses the transcription factor circuits and epigenetic mechanisms that concur to maintain lineage integrity in post-thymic cells and yet allow effector cell differentiation.

► The transcription factors Thpok and Runx3, promote CD4 vs. CD8 cell differentiation in the thymus.
► Thpok and Runx3 are differentially involved in maintaining CD4 and CD8 lineage integrity.
► In CD8 cells, the silencing of CD4-lineage genes has a strong, Runx3-independent, epigenetic component.
► In CD4 cells, CD8-lineage genes are actively repressed at least in part through Thpok.
► Unlike in thymocytes, expression of Thpok and of Runx3 are not mutually exclusive.