A positive look at double-negative thymocytes

Key Points Despite advances in transgenic mouse technology, our understanding of early aspects of T-cell development from CD4 − CD8 − double-negative progenitors in the thymus is still incomplete. As a cell population, double-negative thymocytes are heterogeneous, and a consensus has not been reached on how their content of T-cell progenitors should be identified. Flow cytometry is an ideal experimental approach for the study of lymphocyte development, and, with care, additional information can be obtained regarding lineage inter-relationships of cells. As shown for the analysis of early B-cell development, molecular and cellular approaches at the single-cell level can be applied; similar approaches need to be carried out for the phenotypically defined T-cell progenitor subsets. In some respects, our understanding of the cellular and molecular aspects of early T-cell differentiation is lagging behind that of B cells. Papers describing gene-knockout and reporter-transgenic mice in which thymocyte development is affected are often difficult to interpret. Progress in this field will be hampered unless a more detailed phenotypic and molecular analysis of progenitor thymocytes at the single-cell level is carried out.