Programmed cell death plays an important role during thymocyte development, since a vast majority (97%) of mouse cortical thymocytes die in thymus, whereas only 3% of these cells are rescued from cell death and positively selected. Although it seems well established that thymocyte fate depends upon appropriate surface-expressed T cell receptor, little is known about the molecular mechanism(s) r...

We recently demonstrated the expression of somatostatin (SS) and SS receptor (SSR) subtype 1 (sst1), sst2A, and sst3 in normal human thymic tissue and of sst1 and sst2A on isolated thymic epithelial cells (TEC). We also found an inhibitory effect of SS and octreotide on TEC proliferation. In the present study, we further investigated the presence and function of SSR in freshly purified human th...

The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted...

NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived N...

The CD4(+)CD8(+) (double positive, DP) stage of thymic development is thought to be the earliest period that generates natural Foxp3(+) regulatory T (Treg) cells important for the prevention of autoimmunity. However, we found that most Foxp3(+) DP cells identified by routine flow cytometry represent doublets comprised of Foxp3(-) DP and Foxp3(+) CD4(+)CD8(-) (CD4SP) cells. This was determined u...

Eotaxin has been characterized as a chemokine involved in eosinophil activation; however, mRNA for this C-C chemokine has been shown to be constitutively expressed in thymus. Immunohistochemical analysis showed a punctate distribution pattern, with eotaxin expression localized mainly in the medulla and in Hassle's corpuscles. Moreover, the receptor for eotaxin, CCR-3, was detected on thymocytes...

As T cells develop, they migrate throughout the thymus where they undergo essential bi-directional signaling with stromal cells in distinct thymic microenvironments. Immature thymocyte progenitors are located in the thymic cortex. Following T cell receptor expression and positive selection, thymocytes undergo a dramatic transition: they become rapidly motile and relocate to the thymic medulla. ...

During development, thymocytes express a number of genes typical for activated peripheral T lymphocytes, including granzymes. We have now analyzed by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and cytochemistry fetal liver cells and thymocytes at various developmental stages for the expression of granzyme A-G genes. At days 13-17 of gestation, only granzyme ...

Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T ...

Thymocyte-positive selection is believed to result from low affinity/avidity interactions of TCR and MHC proteins, but how these weak interactions translate into downstream biochemical signals and how such signals modulate gene expression is unknown. Using a culture system where isolated immature thymocytes can be induced to differentiate along the CD4 lineage pathway, we show that sustained lo...