The thymus gland, where T lymphocyte development occurs, is targeted in malnutrition secondary to protein energy deficiency. There is a severe thymic atrophy, resulting from massive thymocyte apoptosis (particularly affecting the immature CD4+CD8+ cell subset) and decrease in cell proliferation. The thymic microenvironment (the non-lymphoid compartment that drives intrathymic T-cell development...

Inhibins and Activins are members of the TGF-β superfamily that regulate the differentiation of several cell types. These ligands were initially identified as hormones that regulate the hypothalamus-pituitary-gonadal axis; however, increasing evidence has demonstrated that they are key regulators in the immune system. We have previously demonstrated that Inhibins are the main Activin ligands ex...

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T-cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indi...

The ordered migration of thymocytes from the cortex to the medulla is critical for the appropriate selection of the mature T cell repertoire. Most studies of thymocyte migration rely on mouse models, but we know relatively little about how human thymocytes find their appropriate anatomical niches within the thymus. Moreover, the signals that retain CD4+CD8+ double-positive (DP) thymocytes in th...

This study aimed to investigate the effects of prenatal nicotine exposure (PNE) on thymocyte apoptosis and postnatal immune impairments in vivo and further explore the epigenetic mechanisms of the pro-apoptotic effect of nicotine in vitro. The results showed that PNE caused immune impairments in offspring on postnatal day 49, manifested as increased IL-4 production and an increased IgG1/IgG2a r...

In this study, we identify transmembrane protein 131-like (TMEM131L) as a novel regulator of thymocyte proliferation and demonstrate that it corresponds to a not as yet reported inhibitor of Wnt signaling. Short hairpin RNA-mediated silencing of TMEM131L in human CD34(+) hematopoietic progenitors, which were then grafted in NOD-SCID/IL-2rγ(null) mice, resulted in both thymocyte hyperproliferati...

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-m...

The peripheral T cell repertoire has been extensively characterized. One of its outstanding features is the phenomenon of major histocompatibility complex (MHC) 1 restriction. Foreign antigens are co-recognized by inducer T cells in association with self-Ia molecules (1, 2). This specificity is dominated by the genetically polymorphic portions of the Class II MHC gene products and is determined...

Many mathematical models have been published with the purpose of explaining aspects of T-cell development in the thymus. In this manuscript we adapted a four-compartment model of the thymus and used a range of mathematical approaches with the aim of explaining the dynamics of the four main thymocyte populations in the mouse thymus, from the emergence of the first fetal thymocyte until the death...

The tyrosine kinase p56lck regulates the differentiation and proliferative expansion of pre-T cells. However, nothing is known about other signaling molecules that operate with p56lck to mediate the pleiotropic changes that occur at this stage of thymocyte development. We used a genetic strategy to examine the requirement for the GTPase Rho in p56lck-mediated signals in the thymus. By generatin...