Volume 10 Issue 6, June 2009

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.

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.

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 (T_H1 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 T_H1 development by suppressing the expression of key T_H1-associated genes and therefore regulates T_H1 cell–mediated colitis.

Toll-like receptor signaling must be carefully regulated to avoid excessive inflammation. O'Neill and colleagues identify a splice variant of the adaptor TRAM that negatively regulates MyD88-independent pathway activated by Toll-like receptor 4.

How and where bacterial recognition triggers the induction of type I interferon is unclear. Teti and colleagues show that phagosomal bacteria trigger Toll-like receptor 7–dependent interferon production in lysosomes of conventional dendritic cells.

Several subsets of Foxp3⁺ regulatory T cells are known to exist. Campbell and colleagues show that one subset of regulatory T cells requires the transcription factor T-bet during T helper type 1–mediated immune responses in vivo.

The function of interleukin 17 in the pathogenesis of chronic inflammatory disorders is controversial. Flavell and colleagues now demonstrate that interleukin 17A mediates a protective effect on T cell—driven intestinal inflammation in vivo.

The function of T cell antigen receptor (TCR) specificity in thymic regulatory T cell development is controversial. Hsieh and colleagues show that this development is a 'TCR-instructive' process that depends on a small selecting niche

The transcription factor ELF4 controls hematopoietic stem cell quiescence. Lacorazza and colleagues show that ELF4 is also needed to maintain the quiescence of naive T cells during steady-state conditions and after antigen stimulation.

The reorientation of the T cell microtubule-organizing center toward the antigen-presenting cell enables the directional secretion of cytokines and lytic factors. Huse and colleagues show that this process depends on diacylglycerol.

Cytotoxic T lymphocytes recognize a restricted set of immunodominant HIV peptide epitopes. Iversen and colleagues show that the cleavage and abundance of HIV peptides are influenced by intraepitope as well as flanking virus escape mutations.

How transcription factor NF-κB influences B cell development remains enigmatic. Rajewsky and colleagues show that NF-κB activation driven by the kinase IKK is required for the generation of B cells expressing immunoglobulin-λ but not immunoglobulin-κ light chains.

Immunoglobulin gene rearrangements occur in an organized, temporal way. Skok and colleagues show that immunoglobulin alleles 'pair' to coordinate cleavage and allelic availability.