The elimination of autoreactive T cells occurs via thymocyte apoptosis and removal by thymic phagocytes, but the sequence of events in vivo, and the relationship between thymocyte death and phagocytic clearance, are unknown. Here we address these questions by following a synchronized cohort of thymocytes undergoing negative selection within a three-dimensional thymic tissue environment, from th...

Successive colonization of the thymus by waves of thymocyte progenitors has been described in chicken-quail chimeras and suggested from studies in mice. In swine, we show that the first CD3epsilon-bearing thymocytes appear on day 40 of gestation (DG40). These early thymocytes were CD3epsilonhigh and belonged to the gammadelta T cell lineage. Mature CD3epsilonhigh alphabeta thymocytes were obser...

Rabbit anti-thymocyte globulin is used worldwide to treat and prevent rejection in kidney transplantation. Multiple mechanisms of action of this polyclonal preparation are responsible for its success. Studies have supported clinical benefits of rabbit anti-thymocyte globulin in high immunological risk kidney transplant recipients when used as an induction agent at the time of transplant and for...

BACKGROUND Thymopoiesis requires thymocyte-stroma interactions and proteases that promote cell migration by degrading extracellular matrix and releasing essential cytokines and chemokines. A role for several members of the A Disintegrin and Metalloprotease (ADAM) family in T cell development has been reported in the past. METHODOLOGY/PRINCIPAL FINDINGS Here, we present data indicating that th...

During thymic T cell development, immature CD4 CD8 double-positive (DP) thymocytes develop either into CD4 CD8 Th cells or CD4 CD8 CTLs. Differentially expressed primary factors inducing the fate of these cell types are still poorly described. The transcription factor Runx3/AML-2 Runx, rust dominant factor; AML, acute myeloid leukemia is expressed specifically during the development of CD8 sing...

Cell adhesion, migration, differentiation and survival or death is amongst a large spectrum of biological responses that can be elicited by ligation of extracellular matrix components to their corresponding receptors. As regards the physiology of the thymus, cell migration is a crucial event in the general process of T cell differentiation. Studies on the intrathymic distribution of ECM compone...

At least three stages in the intrathymic development of pre-T cells are demarcated by differences in the competence to express the interleukin-2 (IL-2) gene as an acute response to stimulation. IL-2 inducibility appears to be acquired relatively early, prior to T-cell receptor (TcR) gene rearrangement. It is then abrogated during the stage when cells are subject to positive and negative selecti...

The thymus is a site of active T-lymphoid cell proliferation and DNA synthesis. In this study, the capacity of human thymocytes for nucleoside transport was assessed both by cytosine arabinoside influx and by equilibrium binding of nitrobenzylmercaptopurine riboside (NBMPR), a specific ligand for the equilibrative nucleoside transporter of leukocytes. The proportion of freshly isolated thymocyt...

The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors ...

Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11.10 T-cell antigen receptor...