Invariant natural killer T cells (iNKT cells) are innate-like T cells important in immune regulation, antimicrobial protection, and anti-tumor responses. They express semi-invariant T cell receptors, which recognize glycolipid antigens. Their positive selection is mediated by double-positive (DP) thymocytes, which present glycolipid self-antigens through the noncanonical MHC class I-like molecu...

Most fetal thymocytes from 14-d mouse embryos are Thy-1+, L3T4-, Ly-2-, and express the receptor for interleukin 2 (IL-2). The development of thymocytes has been followed in fetal thymus organ cultures. When fetal thymus from 14-d embryos were cultured for a 6-d period, thymocytes increased in number 20-40-fold, and 95% became Thy-1+, L3T4+, Ly-2+. The addition of IL-2 to organ cultures of 14-d...

Multiple signaling pathways are known to induce apoptosis in thymocytes through mechanisms that include the loss of mitochondrial membrane potential, cell shrinkage, caspase activation, and DNA degradation but little is known about the consequences of apoptosis on the properties of the plasma membrane. We have previously shown that apoptotic signals, including survival factor withdrawal and glu...

A complete understanding of negative selection has been elusive due to the rapid apoptosis and clearance of thymocytes in vivo. We report a TCR transgenic model in which expression of the TCR during differentiation occurs only after V(D)J-like recombination. TCR expression from this transgene closely mimics expression of the endogenous TCRalpha locus allowing for development that is similar to ...

We have investigated the capacity of our established thymic stromal cell clone (MRL104.8a) or its derived factor(s) to induce the differentiation of immature thymocytes. Culture of purified adult murine double-negative (CD4-CD8-, indicated here as CD4-8-) thymocytes on the MRL104.8a thymic stromal cell monolayer for 1 day resulted in the induction of an appreciable percentage of CD4-8+ thymocyt...

We previously described a fibronectin/VLA-5-dependent impairment of NOD thymocyte migration, correlated with partial thymocyte arrest within thymic perivascular spaces. Yet, NOD thymocytes still emigrate, suggesting the involvement of other cell migration-related alterations. In this context, the aim of this work was to study the role of extracellular matrix ligands, alone or in combination wit...

Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investig...

As we have shown previously, cocultures of bone marrow cells with large numbers of syngeneic thymocytes enhance erythroid colony formation in plasma clots, whereas cocultures with low numbers of thymocytes suppress erythroid colony formation. In this article, we present evidence that the enhancing and suppressing functions of thymocytes are most likely mediated by at least two separate subpopul...

The importance of graft-vs.-host (GVH) activity to the ability of thymocytes to augment hemopoiesis in radiation chimeras was investigated. Parental (P) lymph node cells were found by the 59Fe-uptake method not to have an analogous augmentative effect. When thymus donor, marrow donor, and irradiated recipient were chosen immunogenetically so that GVH could occur in either the presence or absenc...

Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the medulla. CCR7 is pivotal for cortex-to-medulla migration of positively selected thymocytes, and CCR7-mediated migration to the medulla is essential for establishing central tolerance, thereby, preventing tissue...