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More than 20 years after the first successful engraftment of human leukocytes and hematopoietic organs in mice, scientists met for the 2nd International Workshop on Humanized Mice to discuss progress and to highlight expectations in this dynamic field.
While promiscuous expression of tissue-specific antigens (TSAs) in the thymus is essential for self-tolerance, immunologically relevant TSA expression may also occur in the secondary lymphoid organs. A new study links the transcriptional regulator Deaf1 with altered TSA expression in the secondary lymphoid organs and autoimmune diabetes.
Like every metazoan species hosting a gut flora, drosophila tolerate commensal microbiota yet remain able to mount an efficient immune response to food-borne pathogens. New findings explain how the quantity of reactive oxygen species in the gut is 'tuned' to microbial burden and how intestinal immune homeostasis is thereby maintained.
Foxp3 expression is not stable and may be extinguished both in vitro and in vivo in regulatory T cells that convert into proinflammatory effector T cells. The loss of Foxp3 in regulatory T cells under autoimmune conditions may result in the conversion of suppressor T cells into highly autoaggressive lymphocytes.
Macrophages infected with human immunodeficiency virus type 1 emit long intercellular conduits that shuttle the viral protein Nef to bystander B cells, where it impairs cellular function and immunoglobulin class switching.
New work explains how the interferon-γ-regulated GTPase Irgm1 on phagosomes responds to intracellular signaling and recruits the 'machinery' for fusion with lysosomes. This pathway overlaps a signaling route controlled by bacteria to prevent the fusion of phagosomes with lysosomes.
The molecular mechanism by which thymocytes are positively selected remains incompletely understood. Three studies add a new piece to the positive selection puzzle.
Jawless fishes, the 'sister' group of jawed vertebrates, use leucine-rich repeat–containing proteins as antigen receptors. New work shows that the two isotypes of variable lymphocyte receptors are expressed in distinct lymphocyte lineages, which indicates that lymphocytes resembling T cells and B cells are an ancient feature of all vertebrates.
The thymic medulla provides a unique milieu for the induction of T cell tolerance. New work now provides a first glimpse of how thymocytes scan this microenvironment and thus maximize their chances of encountering self antigen.
Tipping the balance of early cytokine production can lead to lineage bias and, potentially, immune-mediated pathology. Mapping of a leishmania-susceptibility region has identified a gene that may determine the extent of T helper type 2 bias in naive helper T cells.
DAP12-coupled receptors influence signals emanating from Toll-like receptors, integrins and receptors for cytokines and growth factors. New findings indicate that DAP12 also facilitates the ability of CSF-1R, the receptor for M-CSF, to induce the stabilization and nuclear translocation of β-catenin.
Dendritic cells are best known as antigen-presenting cells that initiate adaptive immune responses. Three new papers suggest that basophils initiate allergen- and helminth-driven CD4+ T helper type 2 responses by functioning as antigen-presenting cells in draining lymph nodes.
Deficiency in acid sphingomyelinase causes lysosomal storage of sphingomyelin, mediates resistance to stress-induced apoptosis and alters susceptibility to certain infections. New work links acid sphingomyelinase to the granule exocytosis of cytotoxic T cells.
The receptor for the lipid mediator sphingosine 1-phosphate is critical for T cell trafficking. New data show that signaling mediated by this receptor critically controls the development, maintenance and suppressive activity of natural regulatory T cells that express the transcription factor Foxp3.
The evolution of immunodominant epitopes in HIV-1 Gag proteins correlates with quantitative measures of several antigen processing events. Thus, peptides recognized by CD8+ cytolytic T cells are selected by their ability to pass through the antigen processing pathway, as well as by their binding to HLA molecules.
