Reviews & Analysis

In this Timeline article, Shigekazu Nagata and Masato Tanaka highlight some of the key discoveries that have shaped the field of programmed cell death over the past 50 years and explain their relevance for the immune system.

The role of T cell help to B cells was discovered only a few years after the discovery of B cells. In this Timeline article, the author describes the key events that led to the identification of T follicular helper (T_FH) cells as the main T helper cell type for B cells.

As we celebrate 50 years since his seminal Nature paper describing separate lineages for B cells and T cells in the chicken, Max Cooper looks back at the early discoveries that made this breakthrough possible and describes how the B cell field emerged.

The technological revolution in vaccination — from the empirical approach pioneered by Jenner and Pasteur to the recent developments in structural and reverse vaccinology, combined with synthetic biology — promises great hope for the development of safer and more effective vaccines against all infectious diseases.

The molecular cloning of the forkhead box P3 (FOXP3) gene led to a renaissance in the field of suppressor T cells (now known as regulatory T cells). In this Timeline article, the authors describe the key events that demonstrated the importance of FOXP3in immune regulation, starting with the discovery of the scurfy mouse some 65 years ago.

New advances in our understanding of the molecular mechanisms linking cell death and inflammation are discussed in the context of historical studies from the past two centuries.

The mechanisms underlying the antiviral activity of type I interferons (IFNs) are still unclear, but IFNα has long been used in the treatment of chronic hepatitis C (CHC). While reviewing the history of IFNα-based CHC treatment, Markus H. Heim highlights the remaining questions and discusses the future challenges of IFN-based therapies.

The past 15 years have seen a breakthrough in the field of innate immunity. In this Timeline article, the authors discuss the early events that led to the identification of Toll-like receptors as the prototype pattern-recognition receptors that link innate and adaptive immune responses.

The detection of multiple and often rare T cell specificities is crucial for understanding and therapeutically manipulating T cell responses. In this Perspective article, Daviset al. summarize the latest advances in peptide–MHC multimer technology that have rendered peptide–MHC multimers a valuable tool in both basic and clinical T cell research.

In 1950, the function of the thymus was unknown. Jacques F. A. P. Miller describes how research on its immunological role started and gives an overview of the last 50 years of research on the thymus.

The ITN was founded in 1999 with the goal of achieving “... a robust state of immune tolerance in the absence of ongoing immunotherapy while maintaining a competent immune system”. What are the challenges that have been met along the way and the lessons learnt for future translational research?

More than 30 monoclonal antibody-based therapies have been approved for clinical use in the past 25 years. By looking at the strategies that have been used by pharmaceutical companies to develop these products, this Timeline article provides insight into the challenges that will be faced in developing the next generation of therapeutic antibodies.

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.

This Timeline article provides an overview of the discovery and proposed mechanisms of action of aluminium salts, the most widely used vaccine adjuvants. The recent progresses and outstanding controversies on how aluminium salts function as adjuvants are also discussed.

Here, Alan Baxter provides an historical view of experimental autoimmune encephalomyelitis (EAE). Its value in providing insight into T–cell immunology is clear, but might the reductionist approach to EAE have hindered our appreciation of the polyantigenic responses that occur in multiple sclerosis and thereby its clinical relevance?

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.