CD4/CD8-lineage differentiation in the thymus: From nuclear effectors to membrane signals

During thymocyte development, immature thymocytes that express both CD4 and CD8 genes must choose either a helper CD4(+) or cytotoxic CD8(+) T-cell fate. Over the past two years, there have been some important advances regarding T-cell lineage choice, including the identification of transcription factors required for CD4 gene silencing by CD8-lineage cells (RUNX3) or for CD4(+) T-cell differentiation (GATA3), and a better understanding of how T-cell receptor (TCR) signalling correlates CD4/CD8-lineage differentiation to MHC specificity. This review summarizes these recent advances and highlights potential links between TCR signals and nuclear effectors of lineage differentiation.