Reviews & Analysis

In this Opinion article, the authors discuss our current understanding of the roles of immunoproteasomes and thymoproteasomes in T cell receptor repertoire formation and propose that immunoproteasomes have additional roles in cytokine production and T helper cell differentiation.

Unprecedented insight into the early stages of HIV-1 infection has provided important clues for vaccine design. Here, the authors discuss how early virological and immunological events, including transmission by a single founder virus and marked CD4⁺T cell loss, might influence the course of disease.

An important aspect of atherosclerosis is the defective resolution of the inflammatory response to subendothelial lipoproteins. But what are the pathways involved in inflammation resolution, why are they defective in atherosclerotic lesions and how can they be therapeutically targeted?

This Review describes our current understanding of how the 'space' for the peripheral naive T cell pool is influenced by competition for homeostatic signals and how the 'place' at which the T cells encounter these signals can influence their physical and functional maintenance.

This Review discusses the recent studies revealing new roles for endolysosomal proteases in immune cells, as well as their well known involvement in antigen presentation. These include crucial activities in innate immunity, regulation of cell death and control of pathogen invasion.

Recognition of self-peptide–MHC complexes in the thymus is necessary for thymocyte survival, but can also result in cell death. Here, the authors provide a unique insight into this apparent paradox, describing how the repertoire of self-peptide–MHC complexes that support T cell selection is shaped.

These authors propose that the T helper 17 cell and induced regulatory T cell lineages were the first T cells of the adaptive immune system to evolve in vertebrates as a means to counter-regulate immune responses in the gut to foster a large, diverse commensal microbiota for the benefit of the host.

Coeliac disease results from an inappropriate response to dietary gluten. In this Review, the authors describe the ways in which intestinal tissue cells contribute to the inflammatory environment that leads to the induction of a tissue-destructive, gluten-specific T cell response.

Germinal centres are hubs for the generation of long-lived high-affinity antibodies that are necessary for adaptive immunity, but they can also be the source of pathogenic autoantibodies. Here, the authors explore how dysregulation of germinal centres might contribute to autoimmune disease.

Mucosal surfaces are lined by epithelial cells that establish a barrier between external environments and the internal milieu. Recent advances have uncovered mechanisms of barrier regulation by immune stimuli and, conversely, how mucosal immunity is regulated by barrier function.

This Review focuses on the recent studies showing that inhibition of the nuclear factor-κB (NF-κB) pathway in epithelial cells unexpectedly results in the spontaneous development of inflammatory conditions. These results imply a role for NF-κB in these cells in controlling tissue homeostasis rather than promoting inflammation.

T follicular helper cells are strategically positioned in germinal centres and equipped to provide the signals necessary for antibody production by B cells. This Review describes the latest studies that explore their development and function and their relationship with other T helper cell subsets.

This Review proposes an integrated model for the development of follicular versus marginal zone B cells based on the coordination of B cell receptor signal strength with signals through Notch2 and the receptor for B cell-activating factor and signals that are involved in the migration to and retention of B cells in the marginal zone of the spleen.

Time-lapse video microscopy is an important experimental tool for examining the dynamic behaviour of immune cellsin situand involves quantitative analysis of cell migration and cell–cell interactions. Here, several commonly measured parameters and imaging artefacts are described and potential solutions to detect and correct these artefacts are proposed.

The recent re-evaluation of the concept that CD4⁺T helper cell subsets are irreversibly differentiated lineages has become one of the most hotly debated issues in immunology. Here, four leaders in the field provide their thoughts on the complexities and controversies surrounding the functional plasticity of T cell subsets.

The regulation of gene expression at the level of transcription is important for controlling inflammatory responses. Here, the authors describe the key factors and molecular mechanisms involved in this regulation in macrophages and explain how these factors and mechanisms mediate the distinct but coordinated regulation of the different components of the inflammatory response.

Studies in rhesus macaques have been instrumental in driving the progression of potential HIV vaccines to clinical testing. But after two failed clinical trials, David Weiner and colleagues re-evaluate the predictive value of data from this animal model and explain how it might be better used for HIV vaccine development.

Recent advances in the techniques for genetically engineering various lymphocyte subsets hold great promise for cell-based therapies to improve or correct aberrant immune responses. With several new approaches now entering clinical trials, continued efforts will focus on improving their safety and efficacy.

The skin and the immune cells that it contains provide essential protection from injury and infection. This Review describes recent studies that expand our understanding of the functional role of these sentinel cells in sensing danger and mediating homeostasis and disease in the skin.

Bali Pulendran provides a historical overview of the development of the successful yellow fever vaccine. He describes recent advancements in our understanding of its mechanisms of action resulting from the use of systems biological approaches and how this knowledge might be applicable to vaccine development in general.