Abstract
During mammalian T cell development, CD4+CD8+ double-positive (DP) thymocytes must make a lineage choice to become either conventional CD4+ or CD8+ T cells, dependent on their specificity for MHC-II or MHC-I, respectively. Alternatively, DP thymocytes can decide to become innate-like T cells in response to nonclassical MHC-I molecules. A key feature is the downregulation of CD8, which causes transient T cell receptor (TCR) signaling in MHC-I-selected DP thymocytes. Hence, this kinetic signaling model postulates that short or long duration of TCR signals during positive selection can direct the development of cytotoxic or helper T cell lineages. In this opinion article, we discuss the effects of constitutive expression of transgenic CD8 and prolonged TCR signaling on T cell lineage choice in MHC-I selected mouse thymocytes.
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