It is nearly 40 years since Jacques Miller revealed the importance of the thymus as a major primary lymphoid organ. However, despite a vast number of subsequent publications confirming this, and defining many facets of thymopoiesis, it is clear that several key issues have remained unresolved. In order to review the enormous advances made in understanding the life of a T cell from precursor to pathology, the third ‘ThymOz’ meeting has been held in Australia*.
Previously regarded as an adhesive bone matrix protein, recent studies suggest that osteopontin (Eta-1) is also a novel RGD-containing cytokine that regulates early cell-mediated immunity. Proteins related to the extracellular matrix may function as important modulators of immune responses.
The TNF-family molecule osteoprotegerin ligand (OPGL, also known as TRANCE, RANKL and ODF) is a key regulator of bone remodeling and essential for the development and activation of osteoclasts. Intriguingly, OPGL also regulates T cell–dendritic cell communications, dendritic cell survival and lymph-node organogenesis. Here, Young-Yun Kong and colleagues discuss the role of OPGL, and its receptor RANK, in the immune system and in bone metabolism.
An immature CD4+CD8+ thymocyte can differentiate into a functionally specialized CD4+ or CD8+ T cell. The molecular mechanisms underlying this CD4/CD8 lineage choice are poorly understood. Recent evidence suggests that thymocytes are sensitive to subtle variations in signal intensity and that lineage choice might be the consequence of the integration of signals emanating from multiple pathways.
Type I interferons (IFN-1s) activate Stat4 and promote Th1 development in human, but not mouse, CD4+ T cells. Recently, IFN-1-induced Stat4 activation in human cells was found to require interactions of Stat4 with Stat2. A remarkable genetic dissimilarity between murine and human Stat2 explains the ability of human, but not mouse, CD4+ T cells to undergo IFN-1-induced Stat4 activation and Th1 development.
Apoptosis is induced in the course of immune responses to infectious agents. The last step of apoptosis is recognition and ingestion of the dying cells by phagocytes. Here, Marcela F. Lopes and colleagues discuss recent studies and argue that phagocytosis of apoptotic cells plays a previously unrecognized role in regulating the nature of immune responses against pathogens.
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