Opinion

In this Opinion article, the effector function of annexin A1 in the anti-inflammatory action of glucocorticoids is discussed, and a model to address the opposing effects of glucocorticoids on the expression of annexin A1 by different immune cells is proposed.

This article proposes that endogenous peptides can enhance the recognition of antigenic peptides by T cells and, based on results from MHC class I- and class II-restricted T-cell systems, that CD4 and CD8 have different roles in the recognition of endogenous peptide–MHC complexes.

These authors express their opinion that we should devote more research attention to uncovering the mechanisms by which a host can tolerate, as well as resist, infection with a pathogen. New drugs to increase tolerance to infection should provide therapies to which pathogens will not develop resistance.

The activation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors influences signalling pathways downstream of other receptor types. In this Opinion, Lionel Ivashkiv describes how ITAM-dependent signalling can differentially influence cellular responses to Toll-like-receptor ligands and cytokines.

In this Opinion article, Stephen Galli and colleagues discuss the recent evidence that mast cells can have negative, as well as positive, immunomodulatory functions, and suggest that mast cells might have distinct roles at different phases of an immune response.

Accumulating evidence suggests that B cells can regulate immune responses. Here, the authors present a model to explain how B cells may regulate autoimmune pathology by secreting interleukin-10 in response to Toll-like receptor triggering and thereby mediate immune suppression.

Given that T-cell receptor (TCR) repertoires are randomly generated, how come T cells bearing identical TCRs often dominate the response to an antigen in many individuals? Here, the authors provide a molecular explanation to the conundrum of public T-cell responses.

Several models have been proposed to explain how cytotoxic T-lymphocyte antigen 4 (CLTA4) regulates T-cell activation but no model fully accounts for its overall function. Here, Christopher Rudd presents a new reverse stop-signal model, which can potentially explain multiple aspects of CTLA4 function.

Distinct members of the interleukin-12 (IL-12) cytokine family can differentially regulate T-cell-mediated inflammation. In this Opinion article, the authors propose that microbial products and endogenous mediators can control the balance between these cytokines, thereby directly regulating the inflammatory response.

How do antigenic tumour cells and chronic pathogens exploit natural regulatory mechanisms to become non-immunogenic? Andrew Mellor and David Munn propose that such immune unresponsiveness is an indirect consequence of the need to control the potentially lethal consequences of unrestrained immunity to innocuous substances.

In this Opinion article, the authors propose that the immunological process that underlies type 1 diabetes is relapsing–remitting in nature; they highlight the supporting evidence and the remaining controversies, and discuss the possible therapeutic implications of their hypothesis.

Here, the authors propose a new mechanism of immune tolerance. It involves the production of the immunoregulatory enzyme IDO (indoleamine 2,3-dioxygenase) induced by reverse signalling and non-canonical nuclear factor-κB activation in dendritic cells interacting with regulatory-T-cell-expressed co-receptors.

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?

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.

A number of different non-conventional T-cell lineages with innate phenotypes have been identified. As outlined here, it seems likely that 'innate' T cells develop as a result of interactions with non-classical MHC molecules expressed by haematopoietic cells in the thymus.

The DRiP hypothesis proposes that most peptides that bind to MHC class I molecules are derived from newly synthesized defective proteins. Here, the authors revise this hypothesis and propose that some peptides result from the random delivery of unchaperoned nascent polypeptides to the proteasome.

The success and pathogenicity of HIV-1 largely resides in the function of the viral protein Nef. Here, the authors propose that Nef modulates a T cell's ability to form an immunological synapse and modulates T-cell activation to favour viral replication and spread.

The transcription factor forkhead box P3 (FOXP3) is essential for the development and function of regulatory T cells. Here, the authors propose that FOXP3 might also influence how a cell responds to T-cell receptor stimulation and what tissue-homing receptors it expresses.

How can your thymus continue to generate the necessary numbers of CD4⁺CD25⁺ regulatory T (T_Reg) cells once it involutes? Arne Akbar and colleagues propose a model whereby some T_Regcells differentiate from rapidly proliferating memory T cells in the periphery.

The intercellular transfer of cell-surface proteins is known to occur between immune cells, but how common is this occurrence, what are its mechanisms and is it important in influencing the interactions of immune cells?