Reviews & Analysis

The role of the coreceptor CD28 in thymic clonal deletion has been controversial. New evidence suggests that CD28 deficiency impairs the clonal deletion of self-reactive T cells but also results in their developmental diversion to an anergic lineage that ends up in the gut.

A previously unknown protein, Tespa1, that regulates the thymocyte positive-selection checkpoint has now been identified. The phenotype of Tespa1-deficient mice and the role of Tespa1 in thymocyte signaling are very similar to those of Themis-deficient mice and Themis itself, another recently described but unrelated protein.

Protection against recurrent infections requires the generation of memory B cells and persistent antibody production. An adaptor complex of DOCK8-MyD88-Pyk2 now links signaling via TLR9 to activation of the transcription factor STAT3 and the establishment of serological memory.

Immunosurveillance monitors subversion of the endoplasmic reticulum aminopeptidase ERAAP. ERAAP-deficient cells are killed by T cells that recognize nonclassical major histocompatibility complex class I Qa-1 molecules presenting peptides generated in the absence of ERAAP.

Gene profiling by the Immunological Genome Project consortium has identified distinct transcriptional programs that determine the migratory and functional fates of emerging γδ thymocytes.

In the gut, cells of the immune system must tolerate commensal bacteria but also detect pathogens. To achieve this, intestinal phagocytes are hyporesponsive to Toll-like receptor stimulants released from commensals, but can detect invasion of pathogens via the intracellular NLRC4 inflammasome.

Interleukin-17 (IL-17) induces the recruitment of neutrophils to sites of inflammation. In a model of periodontitis, Del-1 is now described to be an inhibitor of IL-17 expression that suppresses the recruitment of neutrophils and the associated inflammation-mediated pathology.

The identification of the natural lipids that select invariant natural killer T cells (iNKT cells) in vivo has been somewhat elusive and controversial. A new study shows that ether-bonded phospholipids, generated mainly in peroxisomes, are responsible for the development of a major subpopulation of iNKT cells.

After class switching in naive B cells, memory B cells and plasma cells that produce immunoglobulin E (IgE⁺ cells) develop through a germinal-center IgE⁺ intermediate cell without an IgG1 phase. In addition, cellular IgE memory resides in IgE⁺ memory B cells, and IgG1⁺ memory B cells are not an important source of IgE memory.

Type 1 diabetes is usually diagnosed after most insulin-producing islets of Langerhans have already been destroyed. However, magnetic resonance imaging can be used to predict the onset of type 1 diabetes, and a benign prognosis correlates with the presence of anti-inflammatory tissue-resident macrophages.

Controversies still surround the cellular and molecular processes involved in the differentiation of hematopoietic stem cells into their mature progeny. New insights into the lineage potential of early thymic progenitors at the single-cell level are presented here.

The invariant chain CD74 prevents the loading of peptides derived from endogenously synthesized proteins onto major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum. CD74 is now shown to serve a similar function for some MHC class I molecules.

Maturation of the proinflammatory cytokine IL-1b is achieved mainly by the canonical caspase-1 inflammasome. An alternative caspase-8-dependent inflammasome that is engaged after stimulation with dectin-1 during fungal and mycobacterial infection has now been described.

Dynamic imaging portrays intraepidermal T cells as truly autoreactive, constitutively transmitting signals from a putative ligand expressed by normal epithelial cells.