The preTCR-dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL-7 signaling.

The requirement for Notch signaling during T-cell development has been extensively studied. Nevertheless, the developmental stage at which it is required and whether additional signaling pathways are needed are still poorly understood. By using a stromal-cell-free culture system, we show that sorted double-negative 3 (DN3) thymocytes only require a Delta-like-4-induced Notch signal to differentiate into double-positive (DP) cells.

Peripheral T cells in the thymus: have they just lost their way or do they do something?

In young adult mice, the thymus produces about a million newly formed T cells every day that colonize peripheral lymphoid tissues. Mostly regarded as a primary lymphoid organ only, the relationship between the thymus and peripheral lymphoid organs is considered unidirectional. However, this perception has been challenged by reports showing that peripheral lymphocytes, mostly T cells, can migrate back into the thymus.

Peripheral T lymphocytes recirculating back into the thymus can mediate thymocyte positive selection.

The thymus continuously produces T lymphocytes that contribute to the maintenance of the peripheral T cell pool. Since peripheral recirculating T cells represent a very minor population among total thymocytes in normal animals, the relationship between the thymus and secondary lymphoid organs is generally considered unidirectional. Recently, several reports have described the presence of recirculating T cells in the thymus, raising issues regarding their possible function.

Regulation of T cell survival through coronin-1-mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering.

T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate.

Early lymphocyte development in bone marrow and thymus.

Haematopoietic stem cells (HSCs), a very rare cell type in the bone marrow, are responsible for the life-long production of all cells of the blood including T and B cells. Until recently, it was thought that the differentiation of HSCs into the various haematopoietic cells was rather hierarchical in that differentiation along a given lineage was associated with a progressive loss of potential to give rise to other blood cell lineages. The recent development of very sensitive and quantitative in vitro assays, together with the identification of new progenitor subpopulations, has challenged this idea.

The sequential determination model of hematopoiesis.

Analysis of hematopoietic development has for decades been central to understanding lineage diversification. Some models consider hematopoietic commitment to be random, and branching lineage maps often include an early myeloid or lymphoid bifurcation. However, the existence of joint lymphoid or myeloid intermediate progenitors argues against both.

Early lymphocyte development in bone marrow and thymus.

Haematopoietic stem cells (HSCs), a very rare cell type in the bone marrow, are responsible for the life-long production of all cells of the blood including T and B cells. Until recently, it was thought that the differentiation of HSCs into the various haematopoietic cells was rather hierarchical in that differentiation along a given lineage was associated with a progressive loss of potential to give rise to other blood cell lineages. The recent development of very sensitive and quantitative in vitro assays, together with the identification of new progenitor subpopulations, has challenged this idea.

Induction of chemokine receptor expression during early stages of T cell development.

The early events in T lineage commitment are difficult to study because of the rarity of these cells. We have therefore used cloned Pax5-/- pre-BI cell lines as a model system to study this. Stimulation in vitro of Pax5-/- pre-BI cells with stromal cells expressing the Notch ligand Delta-like 1 results in them coincidently undergoing some of the phenotypic and functional changes associated with early T cell commitment.

Homeostatic and functional analysis of mature B cells in lambda5-deficient mice.

The peripheral B-cell pool is in dynamic equilibrium and is controlled by a variety of factors. The rate of generation of B cells can influence both the composition and size of the peripheral B-cell compartment. Mice deficient for lambda5 gene expression have a block in early B-cell development leading to a markedly reduced number of peripheral B cells.

A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid developmental potential.

In this report, we identify in the bone marrow (BM) of normal mice a subpopulation of B220+ CD117+ CD19- NK1.1- cells with potent lymphoid and myeloid developmental potential. These cells represent 0.

Differential expression of regulator of G-protein signalling transcripts and in vivo migration of CD4+ naïve and regulatory T cells.

The immune response of T lymphocytes to pathogens is initiated in draining secondary lymphoid organs, and activated cells then migrate to the site of infection. Thus, control of naive and regulatory CD4+ T-cell migration is crucial; however, it is poorly understood in physiological and pathological conditions. We found that CD4+ subpopulations displayed characteristic regulator of G-protein signalling (RGS) gene expression profiles.

Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire.

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements.

A positive look at double-negative thymocytes.

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.