Apoptosis is accompanied by major changes in ion compartmentalization and transmembrane potentials. Thymocyte apoptosis is characterized by an early dissipation of the mitochondrial transmembrane potential, with transient mitochondrial swelling and a subsequent loss of plasma membrane potential (DeltaP sip) related to the loss of cytosolic K+, cellular shrinkage, and DNA fragmentation. Thus, a ...

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide-major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocy...

Zinc porphyrins have anti-inflammatory and anti-allergic properties. The objective of the present study was to characterize the mechanism of zinc tetrakis-(N-methyl-4'-pyridyl) porphyrinato (ZnTMPyP) immune modulation by investigating its effects on the proliferative activity during thymocyte stimulation with mitogenic factors and the molecular events mediating thymocyte proliferation. The resu...

The early growth response (Egr) family of transcriptional regulators consists of four proteins that share highly conserved DNA-binding domains. In many cell types, they are coexpressed and appear to have cooperative roles in regulating gene expression during growth and differentiation. Three Egr proteins, Egr1, Egr2, and Egr3, are induced during thymocyte differentiation in response to pre-TCR ...

The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9(-/-) hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells i...

Cell-cell interactions play a central role during differentiation and development of the immune system. T or B lymphocyte homotypic adhesions can be induced via several surface molecules which, in some cases, are known to trigger the LFA-1/ICAM-1 adhesion pathway. We show here that mAbs reacting with the CD45 common epitopes or restricted RO epitope lead to a strong and rapid aggregation of all...

TCL1, the overexpression of which may result in T-cell leukemia, is normally expressed in early embryonic tissues, the ovary, and lymphoid lineage cells. Our analysis of mouse B-lineage cells indicates that Tcl1 expression is initiated in pro-B cells and persists in splenic marginal zone and follicular B cells. T-lineage Tcl1 expression begins in thymocyte progenitors, continues in CD4(+)CD8(+)...

Antigen-binding diversity is generated by site-specific V(D)J recombination of the T cell receptor (TCR) and immunoglobulin loci in lymphocyte precursors. Coordinate expression of two structurally distinct recombinase activating genes, RAG-1 and RAG-2, is necessary for activation of site-specific V(D)J recombination. In mice bearing targeted disruptions of either the RAG-1 or RAG-2 genes, T and...

The serine/threonine kinase LKB1 is a tumour suppressor that regulates cell growth, polarity, and proliferation in many different cell types. We previously demonstrated that LKB1 controls thymocyte survival via regulation of AMPK activation. In this study, we show that LKB1 was also involved in thymocyte positive selection through regulation of T cell receptor (TCR) signalling. Both LckCreand C...

Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in the thymus. Although glucocorticoids are usually considered immunosuppressive, there is also evidence that they play a positive role in thymocyte selection. To address the question of how endogenous glucocorticoids might influence the adaptive immune response, we generated GRlck-Cre mice, in which the glucocorticoi...