Opinion

Reiner and Adams propose a deterministic scenario for diversifying the fates of the cellular progeny of a single antigen-selected lymphocyte, with an element of plasticity based on the nature of the pathogen and the number of responding cells.

Studies in mice indicate that targeting antigens to dendritic cells (DCs) can elicit strong CD4⁺T cell responses. In this Opinion article, the authors summarize the existing DC-targeting approaches; they discuss whether these vaccines are superior to current vaccines and what future studies should entail to successfully introduce these vaccines into a clinical setting.

Recent evidence indicates that adaptive T cell-mediated immune responses can regulate innate lymphocytes (natural killer cells and innate lymphoid cells) in an interleukin-2-dependent manner. The authors propose a model in which adaptive T cells function as peripheral antigen-specific sensors that recruit and activate innate lymphocytes to amplify and coordinate local immune responses.

Natural killer T (NKT) cell defects have been implicated in several diseases such as autoimmunity, asthma and cancer, but will targeting them really be of clinical benefit? Here, the authors investigate this question and conclude that more careful studies are needed before the true clinical potential of NKT cell-targeted therapies can be determined.

Cells of the mononuclear phagocyte system (MPS) are usually defined by particular functional or phenotypical characteristics. However, this has led to confusion in the field, as many of the criteria that are used to define a particular cell population may actually be shared with other cell types. In this Opinion article, the authors propose that a new nomenclature that is based on cell ontogeny could enable a more robust classification of MPS cells.

Three models have been proposed to explain the link between T cell division and differentiation — epigenetic changes, asymmetric division and the direct regulation of gene expression by cell cycle factors. In support of the third model, this Opinion article describes cell cycle-independent roles for the cyclin-dependent kinases as regulators of immunologically relevant transcription factors.

The age-related involution of the thymus is associated with impaired cellular immunity and it is possible that restoring the thymopoietic activity of the thymus could have medical benefits. In this Opinion article, the authors discuss the development, involution and regeneration of the thymus and highlight the major gaps that still remain in our understanding of these processes.

In this Opinion article, the authors provide an overview of the recent work that has been carried out investigating broadly neutralizing HIV-1 antibodies and their thoughts on the future prospects of the antibody-based prevention of HIV-1 infection.

In this Opinion, the authors provide their perspective on how the type 2 immune response may have evolved and how it functions to mediate both resistance and tolerance to tissue-destructive helminths. They propose that the damage induced during helminth migration and the subsequent need for tissue repair have been major factors in driving the evolution of the type 2 response.

If an exogenous antigen such as gluten can drive the autoimmune features of coeliac disease, such as the production of autoantibodies and the destruction of a specific tissue type, should we be looking more closely at the possibility that other autoimmune diseases are driven by exogenous, not self, antigens?

In this Opinion article, the authors present a model of the barrier systems that control immune cell access to immune-privileged sites. They suggest that immune cell trafficking through 'true' endothelial barriers in the parenchyma results in destructive inflammation, whereas 'educational' epithelial gates allow for selective trafficking to facilitate immunosurveillance of these sites.

Lynda Stuart and colleagues discuss the ability of animals to sense perturbations in host cells caused by pathogen effectors. On the basis of recent mechanistic evidence, they suggest that such effector-triggered immunity might be as widespread in animals as in plants.

The role of natural killer (NK) cells in both immunity to infection and reproductive success is postulated to have placed competing demands on the evolution of NK cell receptors and their MHC class I ligands during the migration of humans out of Africa.

There has been a tendency to associate the development of distinct CD4⁺T cell subsets with the expression of 'master regulator' transcription factors. Here, the authors discuss the shortcomings of this model and explain why 'lineage-specifying' may be a more fitting way to describe these key transcription factors.

In this Opinion, the authors describe an unconventional form of peptide recognition that can allow potentially autoreactive CD4⁺T cells to escape thymic regulation. They explain how these T cells respond to unstable peptide—MHC complexes that evade H2-DM-mediated editing, and they discuss the implications for autoimmunity.

T cells must recognize a vast array of potential foreign peptide–MHC complexes. Comprehensive immune cover can only be provided if each T cell recognizes numerous peptides. The implications of this T cell cross-reactivity include autoimmune disease but also provide opportunities for multiple therapeutic interventions.

The development of effective antiretroviral therapies has greatly improved the disease prognosis for patients with HIV. However, the limitations of these therapies have renewed interest in developing alternative treatment strategies. Here, a group of experts from the International AIDS Society discuss the research steps that need to be taken to achieve the ultimate objective — a cure for HIV.

In this Opinion article, Blander and Sander examine how the immune system is able to distinguish between viable and dead, pathogenic and non-pathogenic, or invading and colonizing microorganisms. They propose five immune checkpoints that can be used to determine the relative threat of a particular microbial encounter.

In this short Perspective article, Glenn Dranoff summarizes the strengths and limitations of three of the most commonly used mouse tumour model systems for investigating host antitumour immune responses and the potential clinical efficacy of novel immunotherapies.

This article discusses the evidence in support of the simultaneous activation of angiogenesis and immunosuppression in a homeostatic tissue repair programme and proposes that these normal biological processes are co-opted by tumours to enhance tumour growth.