Volume 10 Issue 8, August 2009

By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown components of biological pathways. This commentary provides general guidelines for using such screens to answer questions of immunological interest.

The molecular mechanism by which thymocytes are positively selected remains incompletely understood. Three studies add a new piece to the positive selection puzzle.

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.

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 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.

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.

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.

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, T_H-22 cells, that secrete interleukin 22.

Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, T_H-22 cells, that secrete interleukin 22.

Mouse strains show varying inherent biases to T helper type 2 (T_H2) responses. Bix and colleagues identify Mina, a jumonji C protein, as a negative regulator of the gene encoding interleukin 4 whose expression inversely correlates with T_H2 bias.

Tonic antigen receptor signaling contributes to the homeostasis of naive lymphocytes. Alarcón and colleagues show that resting lymphocytes transmit tonic antigen receptor signals through the GTPase TC21 to trigger the PI(3)K pathway.

Mature B cells express immunoglobulin D, but its function is unknown. Cerutti and colleagues show that respiratory mucosal B cells secrete immunoglobulin D, which activates basophils and enhances antimicrobial function.

Macrophages infected with virulent Mycobacterium tuberculosis die by necrosis. Remold and colleagues show that virulent M. tuberculosis promotes necrosis by damaging the plasma membrane and inhibiting its repair.

Immunity-related GTPase 1 (Irgm1) is needed for defense against bacteria that reside in phagosomes of macrophages. MacMicking and colleagues identify molecular mediators that act 'upstream' and 'downstream' of Irgm1 in the phagosomal membrane.

Apoptosis of Mycobacterium tuberculosis (Mtb)-infected macrophages restricts the spread of infection. Basu and colleagues delineate the signaling pathway needed for death of Mtb-infected cells.