Reviews & Analysis

The behaviour of a T cell is moulded by numerous signals encountered during the T cell's life. This Review describes the current technologies that allow the fate and history of individual T cells to be monitored, providing insights into the kinship and prior functional activity of T cell subsets.

The vertebrate adaptive immune system is defined by antigen-binding receptors of diverse specificity and the cells that express them. But how did this system evolve? Here, our current understanding of the evolutionary acquisition of the factors required to generate such receptor variation and cellular complexity is discussed.

This Review describes the mechanisms by which the X chromosome regulates immune responses. The authors discuss how the effects of this chromosome can account for many of the immunological differences, such as altered susceptibility to infection or autoimmune disease, that occur between the sexes.

This Review emphasizes the clinical and immunological insights that can be gained from recent immunotherapy trials in patients with prostate cancer and how these might apply to developing immunotherapies for other types of solid tumour.

A complex and highly regulated pathway ensures that the delivery of cytotoxic cargo of cytotoxic lymphocytes is appropriately aimed and timed. As reviewed here, the study of patients and mutant mice with cytotoxicity defects has revealed many of the molecules involved in this targeted exocytosis of cytotoxic granules.

A comprehensive description of the many ways in which TGFβ can inhibit antitumour immune responses through effects on innate and adaptive immune cells and how these immunosuppressive effects could be targeted for the benefit of patients with cancer.

Here, the authors describe the complex interactions between cells of the innate immune system, the implications of these interactions for activation of adaptive immune cells and pancreatic β-cell death and the impact of infectious agents on these processes.

How can infection with the same virus have different outcomes in different individuals? Here, the authors describe how the outcome is influenced by virus properties, the circumstances of infection and host factors, such as immune regulatory mechanisms and genetic susceptibility.

In this article, the authors describe the development, phenotype and suppressive function of human regulatory T cell populations. There has been much emphasis on the clinical use of these cells, and the associated progresses and pitfalls are discussed here.

The discovery of IL-17-producing T cells has revolutionized our understanding of autoimmune diseases. However, much of the IL-17 released during an immune response is produced before T cells can be activated. Here, Daniel Cua and Cristina Tato describe the cellular sources, transcriptional regulation and physiological relevance of this early IL-17 production.

γδ T cells have innate cell-like attributes that allow them to rapidly produce cytokines and become cytotoxic in response to cell stress and infection. Here, the authors describe how they acquire these effector functions through both developmental programming and polarization in the periphery.

This Review article discusses how the interaction of neutrophils, monocytes and macrophages is important for both initiating and terminating an inflammatory response. The authors describe the phagocyte-derived mediators involved in these interactions and highlight the therapeutic potential of targeting them.

The activation of cytotoxic T lymphocytes by cross-presented antigen (known as cross-priming) is necessary for immunity against certain viruses, bacteria and most tumours. Here, the underlying cellular and molecular mechanisms of cross-priming are described, providing insight into some central questions on the basic mechanisms of cross-priming, and its physiological and therapeutic importance are discussed.

Several distinct populations of dendritic cells and macrophages are found in the intestinal lamina propria; these cells have crucial roles in both tolerogenic and inflammatory-type immune responses at the mucosa. This Review describes the recent findings that have increased our understanding of the origin and functions of intestinal mononuclear phagocytes.

In this Review the authors describe the key attributes of mast cells that make them well suited to initiate and coordinate innate and adaptive immune responses to pathogens, by acting as pathogen sensors, immune effectors and immune modulators.

This Review describes new roles for the tyrosine kinase SYK in innate recognition of pathogens and tissue damage, cell adhesion, bone metabolism and vascular development, and it discusses the emergence of SYK as a promising therapeutic target in autoimmune diseases and B cell lymphomas.

Monoclonal antibodies have shown considerable success as cancer therapeutics. This Focus article describes how these molecules promote tumour eradication by targeting the tumour itself or by targeting cells of the immune system. The authors also discuss the clinical potential of new antibody therapies.

This Review article describes how a subset of nuclear receptors can antagonize pro-inflammatory gene expression, through transrepression mechanisms in macrophages and microglia, and regulate the differentiation and activation of inflammatory helper T cells, particularly T helper 17 cells.

FcγRIIB is the only inhibitory Fc receptor for IgG, common genetic variants of which are associated with susceptibility to autoimmune disease but, also, with protection from severe malaria. Furthermore, understanding the function of FcγRIIB has important implications for the use of therapeutic antibodies.

Therapeutic antibodies have already improved the lives of many people living with autoimmune diseases such as rheumatoid arthritis and Crohn's disease. But there is still room for improvement. Here, the authors review how the current therapeutic antibodies work and how they might be enhanced to increase efficacy and extend their use.