CD4CD8

CD4CD8, typically referred to as double-positive CD4+CD8+ thymocytes, are immature T cells that express both CD4 and CD8 co-receptors. They arise during T cell development in the thymus from precursors that migrate to the thymic cortex. At this DP stage, thymocytes rearrange their T cell receptor (TCR) genes and express the pre-TCR/CD3 complex, along with CD4 and CD8, CD2 and other surface markers. The double-positive population is a major fraction of thymocytes during a critical window of development.

Positive selection occurs in the thymic cortex and is driven by interactions between the thymocyte TCR and self-peptide–MHC complexes presented by thymic epithelial cells. If a DP cell’s TCR recognizes self-MHC with appropriate affinity, it receives survival signals and becomes a single-positive T cell: CD4+ helper T cells if the TCR is MHC class II–restricted, or CD8+ cytotoxic T cells if the TCR is MHC class I–restricted. Cells with too little affinity for self-MHC die by neglect, while highly self-reactive cells may undergo negative selection and be deleted to prevent autoimmunity.

Downstream maturation involves downregulation of one co-receptor, yielding mature CD4+ or CD8+ single-positive T cells that exit to the periphery. DP thymocytes thus provide a key checkpoint and source for the mature T cell repertoire, enabling both lineage commitment and tolerance.

In clinical contexts, immature double-positive phenotypes can appear in certain T-cell leukemias and lymphomas, where flow cytometry may reveal concurrent CD4 and CD8 expression alongside other T-lineage markers.