Review Articles in 2006

Statins are best known as cholesterol-lowering drugs but increasing evidence indicates that they might be an effective treatment for autoimmune disease. Their ability to inhibit post-translational protein prenylation could be key to their immunomodulatory effects.

Although the discontinuation of a clinical trial of amyloid-β vaccination of subjects with Alzheimer's disease led us to reassess the use of immune-based therapy for this disease, subsequent work involving antibody and cell-based therapies looks promising.

This Review discusses recent studies that have identified ways to increase the antitumour response of autologous tumour-reactive cells adoptively transferred to individuals with cancer, such as the use of lymphodepleting regimens before adoptive cell transfer.

The use of antibodies as therapeutic agents is a big business, with 18 now approved for use in the United States. How they are generated and optimized to increase efficacy and safety is the focus of extensive research efforts, which are reviewed here.

Clinical trials of reagents that target B cells in individuals with autoimmune disease, in particular rheumatoid arthritis, have yielded highly promising results. Might such an approach bring us closer to the goal of re-establishing immune tolerance in these individuals?

The caspase family has traditionally been divided into two groups: those involved in regulating apoptosis and those involved in regulating inflammation. However, as discussed in this Review, recent data indicate that capases can also regulate immune-cell development, activation and differentiation.

Regulatory T cells have a role in suppressing immune responses against tumours. Here, Weiping Zou reviews the nature of these cells, how they affect current therapeutic protocols and the ways in which their effects can be modified to improve antitumour immunity.

Evidence for crosstalk between the central nervous system and innate immune cells is accumulating. As discussed by Esther Sternberg, neural factors that first amplify and then temper pro-inflammatory responses have a crucial role in pathogen defence and in preventing toxic shock.

This Review describes how tonic signalling — ligand-independent signalling from Igα–Igβ-containing receptors, such as the pre-B-cell receptor (pre-BCR) and BCR — differs from ligand-dependent signalling and then outlines recent advances in our understanding of how tonic signalling is initiated and regulated.

MHC class II molecules are important factors that contribute to the susceptibility of an individual to autoimmune disease. Jones and colleagues look for clues to their involvement in disease by analysing crystal structures of peptide–MHC-class II complexes.

Control of virus infection usually requires both cellular and humoral immune responses. This Review outlines the role of virus-specific antibodies in combating viral infections, using lymphocytic choriomeningitis virus as a model non-cytopathic virus and vesicular stomatitis virus as a model acutely cytopathic virus.

Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling. However, this Review discusses new data indicating that cFLIP is also required for the survival and proliferation of T cells following T-cell-receptor stimulation.

The authors of this article describe the role of tertiary lymphoid organs in sustaining chronic inflammatory disease and compare the induction and function of such lymphoid neogenesis with that of conventional secondary lymphoid organs.

The CATERPILLER family of proteins, like the mammalian Toll-like receptors, are sensors of microbial products and regulators of the immune reponse. Genetic defects in CATERPILLER genes are associated with various immunological disorders, including hereditary periodic fevers, indicating that CATERPILLERs are important in regulating inflammatory responses.

This article provides an overview of the mechanisms by which eukaryotic cells sense and respond to chromosomal double-stranded DNA breaks and describes the importance of this response for the development of lymphocytes and the development of effective innate and adaptive immune responses.

This article aims to educate immunologists about the key role of neutrophils in the initiation of immune responses, and it describes how, in contrast to conventional wisdom, neutrophils mount responses specific to their environment, making them potential targets to treat inflammation.

Mast-cell activation is a key event in allergic reactions and largely results from signalling through the high-affinity receptor for IgE. However, complementary signalling pathways might also influence mast-cell-mediator release and might be activated by other receptors, such as KIT.

Mucosal immunization could be our best hope for protection against pathogens that infect mucosal tissues. Here, the authors describe how our accumulating knowledge of the mechanisms of mucosal immune defence is being applied to mucosal vaccine design, in particular against HIV.

As thymocytes travel through the thymus, they not only receive signals from stromal cells but also deliver signals to stromal cells to generate the appropriate stromal environment. Takahama describes the factors involved in this lympho–stromal crosstalk for thymocyte trafficking and T-cell-repertoire selection.

All cells of the immune system are derived from precursor cells in the bone marrow known as haematopoietic stem cells (HSCs). This Review describes recent advances in our understanding of the specialized bone-marrow niches that regulate HSC differentiation and self-renewal.