Volume 14 Issue 11, November 2013

A signaling module consisting of the adaptor ADAP and the Carma1–Bcl-10–MALT1 (CBM)–TAK1 signalosome has been shown to selectively induce cytokine secretion but not cytotoxicity in natural killer cells.

Distinct lineages of natural killer T cells arise in the thymus and are characterized by the signature transcription factors T-bet, GATA-3 or RORγt.

In a phosphorylation-dependent positive feedback loop, the cytidine deaminase AID amplifies the generation of double-strand DNA breaks, which shows it can also function downstream of deamination.

The hypoxia-inducible factor (HIF) pathway controls diverse aspects of the immunological response. Enhanced HIF activity is able to extend and potentiate the effector response of CD8⁺ T cells against chronic infections and tumor growth.

Under natural conditions, infections never occur in isolation, yet immunologists rarely consider the immunological outcome of multiple infections. In this Review, Gause and colleagues discuss how helminth infection affects antibacterial and antiviral responses.

Effector responses of NK cells occur via cytoxicity and cytokine secretion. Malarkannan and colleagues identify a signaling module that selectively controls the cytokine production of NK cells.

How γδ TCRs bind antigen presented by antigen-presenting molecules remains unclear. Godfrey and colleagues describe a population of human γδ T cells that interacts with CD1d and provide a molecular basis for how a γδ TCR binds CD1d–α-GalCer.

Mature invariant natural killer T cells (iNKT cells) are an early innate source of cytokines. Hogquist and colleagues classify three lineages of iNKT cells by their distinct transcription factors and cytokine profiles.

Clonal expansion of cytotoxic T lymphocytes entails profound energetic demands. Kallies and colleagues show that the transcription factor IRF4 is critical for the metabolic reprogramming, survival and effector function of these cells during clonal expansion.

S1P₁ is a sphingosine phosphate receptor expressed on lymphocytes. Han and colleagues show that phosphorylated S1P₁ accumulates in brain lesions of patients with multiple sclerosis. Similarly, mice bearing mutant S1P₁ develop more severe experimental autoimmune encephalomyelitis.

The transcription factor HIF is induced in response to hypoxic stress, TCR activation and cytokines. Goldrath and colleagues show that HIF signaling enhances CTL effector responses and can render cells refractory to immune exhaustion.

The cytidine deaminase AID mediates immunoglobulin class-switch recombination. Chaudhuri and colleagues show that a phosphorylation-dependent positive feedback loop regulates AID activity and is initiated by DNA breaks.

Intergenic long noncoding RNAs (lincRNAs) regulate gene expression in various tissues. Zhao and colleagues identify 1,524 lincRNA clusters in thymocytes and mature T cell subsets and reveal dynamic and cell-specific patterns of lincRNA expression during T cell differentiation.