A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry

Chemokines: A New Classification System and Their Role in Immunity

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identified as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-deficient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-deficient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis

https://www.cell.com/cell/pdf/0092-8674(92)90123-T.pdf

Induction of apoptosis in fibroblasts by c-myc protein

The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.

It has been reported that, following the initial expression of the T cell receptor (TcR) alpha/beta, newly generated thymocytes pass through a developmental window characterized by ineffective coupling between the alpha/beta and CD3 components resulting in resistance to deletion (negative selection). However, we now provide evidence that the TcR alpha/beta on developing thymocytes is capable of delivering deletional signals in response to the superantigen staphylococcal enterotoxin B (SEB) as soon as the receptor is expressed. We also show that if TcR+ thymocytes are allowed to mature in organ cultures of embryonic thymus before SEB is added, they respond by proliferation giving rise to blast cells of CD4-CD8-, CD4+CD8- or CD4-CD8+ phenotypes.

Newly generated thymocytes are not refractory to deletion when the α/β component of the T cell receptor is engaged by the superantigen staphylococcal enterotoxin B

The role of the thymus during T-lymphocyte development in vitro.

Following their migration into the thymus, hemopoeitic stem cell precursors enter a complex developmental pathway involving proliferation, differentiation and alphabetaT-cell receptor (alphabetaTCR)-mediated selection procedures, in order to generate mature T-cell populations ready for export to the periphery. Thus, a critical stage during intrathymic T-cell development involves the generation of functionally mature CD4+8- and CD4-8+ cells from immature CD4+8- precursor thymocytes, a poorly understood process referred to as positive selection. While interactions between the alphabetaTCR and MHC-peptide complexes are known to be essential for the initiation of positive selection, additional unknown signals are also required. Using an in vitro reaggregate thymic organ culture system which allows comparison of the abilities of various cell types to induce maturation of CD4+8+ precursors, we provide evidence that both MHC-peptide complexes and specialised accessory molecules must be provided by thymic epithelium for efficient mediation of positive selection. Moreover, analysis of positive selection in the presence of thymic and non-thymic stromal cells expressing MHC class II molecules with the same limited peptide array suggests that this unique ability of thymic epithelium to mediate positive selection of CD4+8- cells is not solely due to presentation of a specialised peptide repertoire, but is dependent upon provision of specialised accessory interactions.

Eric J. Jenkinson

Papers

Newly generated thymocytes are not refractory to deletion when the α/β component of the T cell receptor is engaged by the superantigen staphylococcal enterotoxin B

The role of the thymus during T-lymphocyte development in vitro.

Specialisation of thymic epithelial cells for positive selection of CD4+8+ thymocytes.

Piecing together the thymic puzzle.

PDGFRα-expressing mesenchyme regulates thymus growth and the availability of intrathymic niches. Commentary