A role for glucocorticoids in thymopoiesis has been suggested by studies using glucocorticoid receptor (GR) anti-sense transgenic mice, glucocorticoid synthesis inhibitors and GR antagonists. Unfortunately, no consensus has been reached on exactly how glucocorticoids influence T-cell development. The most recent approach, using GR knockout (GR−/−) mice, indicates that GR signaling is, in fact, dispensable in this entire process.
The complement system is established as a major homeostatic system and a factor in diverse pathologies. Some 500 delegates attended a recent meeting1 to discuss the latest findings in complement research, ranging from studies in sea squirts through to therapeutic trials of inhibitors. Here, we review some of the key topics discussed at the workshop.
A recent meeting* illustrated the extensive cross-talk that exists between adhesion receptors, G-protein-coupled chemokine receptors, growth factor receptors and cell surface proteinases.
Ena Wang and Francesco Marincola propose a novel strategy whereby tumor–host interactions are studied within the melanoma microenvironment by serial gene expression analysis. Methodological constraints and ways to circumvent them are discussed. This approach might improve our understanding of the molecular basis of tumor regression in response to immune manipulation.
How is signaling specificity achieved by the pre-TCR during selection of T-cell fate? Like the TCR, this receptor controls many functions, and recent studies define which pathways couple the pre-TCR to the molecular events controlling survival, proliferation, allelic exclusion at the TCRβ locus, and further differentiation.
Natural or spontaneous antibodies are an essential part of the first line of defense against hematogenically spreading infections, including viruses. These antibodies target virus–antibody complexes and complement to the spleen. This prevents infections from reaching vital organs and enhances neutralizing antibody responses, particularly when the antibody is bound to a highly repetitive antigen.
Adapters can be defined as proteins that mediate intermolecular interactions within a signal transduction pathway and that lack both intrinsic enzymatic and transcriptional activity. Their essential role in lymphocyte signaling was revealed by recent analyses of mice and cell lines deficient in LAT, SLP-76 and BLNK. These and other adapters nucleate signaling complexes and facilitate coupling of antigen receptor triggering to functional responses in lymphocytes.
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