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Fifty years after F. Macfarlane Burnet published his seminal paper on the clonal-selection theory of antibody diversity, six key scientists provide their thoughts and opinions on how this theory was received and how it has helped to shape immunology as we know it today.
Natural killer (NK) cells perform multiple functional activities, including rapid cytokine production and spontaneous cytotoxicity. James Di Santo and colleagues review the evidence that such functional heterogeneity arises from the development of diverse NK-cell subsets with unique biological roles.
To get to the site of inflammation, leukocytes must first adhere to and traverse the blood-vessel wall, events that occur in a cascade-like manner. But what are the exact steps in this cascade and what molecules are involved?
Although best known for its role in mother-to-child IgG transfer, new roles for the neonatal Fc receptor for IgG (FcRn) are emerging. Its role in regulating serum antibody half-life in adults has important implications for autoimmune diseases and antibody-based biologicals.
Recently, two key regulators of calcium influx in lymphocytes were discovered — STIM and ORAI. How this has advanced our understanding of calcium signalling in lymphocytes and the pathological consequences of disruption of this pathway are discussed in this Review.
Hedgehog signalling proteins, and in particular sonic hedgehog, have a role in T-cell development in the thymus and in peripheral T-cell activation, but, as outlined here, some aspects of their functions remain controversial.
Therapeutic strategies that induce antigen-specific immune tolerance without suppressing the ability of the immune system to respond to infectious agents are needed for the treatment of autoimmune diseases. But how might these antigen-specific therapies induce tolerance and are they safe for use in the clinic?
The activating receptor NKG2D (natural-killer group 2, member D) recognizes an array of ligands that are upregulated by cellular stress. But what value is it for the host to express so many ligands for one receptor, and what drives NKG2D-ligand diversity?
In this Viewpoint article, four leading researchers provide their view on the prospect of using tolerogenic cells as an immunotherapy in humans and highlight some of the hurdles that must be addressed for this type of treatment to become a viable therapeutic approach.
Preclinical studies provide hope that the adoptive transfer of regulatory T cells can be used to treat autoimmunity and prevent transplant rejection. Will such an approach ever be feasible in humans? And which regulatory T-cell subset should we use?
Diane Mathis and Christophe Benoist describe how our understanding of the function of autoimmune regulator (AIRE) has developed over the last decade, from its discovery to its role in central tolerance. Key questions that need to be addressed over the next decade are also highlighted.
How self-reactive B cells can exist in the periphery yet be unresponsive to antigen stimulation is unclear. John Cambier and colleagues describe the mouse models that have been used to study B-cell anergy and the possible mechanisms that explain this phenomenon.
CD3-specific monoclonal antibodies have great potential as therapeutics for autoimmune diseases through the induction of immune tolerance. This Review discusses the current progress of the use of these antibodies in preclinical and clinical studies and highlights ways to improve on this type of immune therapy.
Tolerogenic dendritic cells (DCs) have potential as therapeutic tools for preventing transplant rejection. This Review describes what constitutes a tolerogenic DC, how tolerogenic DCs can be induced, the mechanisms by which they mediate tolerance and the future challenges facing DC-based immunotherapy.
Understanding the state of long-lived functional unresponsiveness of T cells, known as T-cell anergy, could help to prevent T-cell-driven autoimmune diseases. This Review discusses the molecular mechanisms underlying this phenomenon and, in particular, the role of E3 ubiquitin ligases.
Owing to recent advances in imaging technology, the behaviour of B cells in germinal centres can now be visualized in three dimensionsin vivo. What have we learnt from such studies and how might this change our understanding of antibody affinity maturation?
What determines whether a T cell lives or dies? And how are the signals that induce apoptosis regulated? Here, Peter Krammer and colleagues discuss the most recent advances in our understanding of the molecular switches that regulate life and death in T cells.
Could xenotransplantation using pigs as the transplant source solve the severe shortage of human organ donors? This Review describes the recent advances that are helping to bring this approach closer to the clinic and the obstacles that still need to be overcome.
What is immune computing? Can the immune system compute? Does it use a computational strategy to function? In this Opinion article, Irun Cohen proposes that the answer to these questions is yes, and applies these ideas to different types of immunity.
Several diseases are associated with reduced numbers of natural killer T (NKT) cells. The authors of this Review ask what drives NKT-cell development in the thymus and what factors ensure NKT-cell survival, maturation and function in the periphery?
