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Self-reactive thymocytes are eliminated through negative selection in the thymic medulla. Robey and colleagues find that autoreactive thymocytes show slower and more confined migration than that of polyclonal thymocytes in the medulla.
Granules containing perforin and granzymes are secreted from cytotoxic T lymphocytes. Krönke and co-workers find that acid sphingomyelase is needed for granule shrinkage just before exocytosis in this process.
Complement forms an ancient innate immune defense. Gros and colleagues provide new insight into the interactions between complement convertase C3b and its regulator factor H and with the staphylococcal inhibitor SCIN.
Macrophage colony-stimulating factor (M-CSF) induces the proliferation of mononuclear phagocytes, and DAP12 is needed for their function. Colonna and colleagues show that DAP12 is also needed for M-CSF-induced stabilization of β-catenin.
Immunological synapses (IS) involving surface receptors form between dendritic cells (DC) and T cells. Rodriguez-Fernandez and colleagues show that IS-induced signals activate Akt and NF-κB and suppress Foxo1 to promote DC survival.
Complement forms an ancient innate immune defense. Gros and colleagues provide new insight into the interactions between complement convertase C3b and its regulator factor H and with the staphylococcal inhibitor SCIN.
Immune complexes are captured from lymph by subcapsular macrophages. Cyster and colleagues show that an intricate relay shuttles antigen into germinal centers to drive affinity maturation.
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.
T helper type 1 cells (TH1 cells) serve a dominant function in T cell–mediated colitis. New work reports that interleukin 17A, an effector cytokine required for the development of autoimmune tissue inflammation, directly inhibits TH1 development by suppressing the expression of key TH1-associated genes and therefore regulates TH1 cell–mediated colitis.
Regulatory T cells have the remarkable ability to suppress immune responses driven by different types of effector T cells. Two recent studies, documenting important functions for T-bet and IRF4 in regulatory T cells, demonstrate that this ability requires the expression of transcription factors typically associated with effector T cell function.
T cell antigen receptor (TCR)-transgenic models have been enormously influential in studies of T cell development in the thymus, particularly in terms of positive and negative selection. New transgenic mice produced with TCR genes cloned from regulatory T cells show that TCR specificity does 'instruct' regulatory T cell fate, within limits.
Jan Vilcek relates how his work helped to identify some of the pleiotropic actions of tumor necrosis factor and contributed to the development of infliximab, the first medically useful tumor necrosis factor antagonist.
How have women fared at Harvard since the events of four years ago? Here, Judy Lieberman and Laurie Glimcher reflect on progress made and barriers still to be breached.
E3 ubiquitin ligases are critical for innate and adaptive immunity. Cao and colleagues show that the E3 ubiquitin ligase Nrdp inhibits the production of proinflammatory cytokines while promoting the release of interferon-β in Toll-like receptor–triggered macrophages.