Volume 14 Issue 2, February 2013

Signaling via the complement factors C3a and C5a regulates effector T cell responses. Evidence now links the absence of local complement activation with a default pathway that leads to the polarization of Foxp3⁺ regulatory T cells.

Maintenance of the peripheral naive CD8⁺ T cell pool depends on T cell antigen receptor (TCR) signals and interleukin 7 (IL-7). TCR signaling limits the duration of IL-7 signals to avoid an interferon-γ-mediated mechanism of apoptotic death of naive CD8⁺ T cells.

Severe intestinal pathology associated with infection with Toxoplasma gondii is a result of the loss of Paneth cells, an unexpected side effect of the secretion of IFN-γ by protective CD4⁺ T cells in the intestinal mucosa.

Double-negative (DN) thymocytes depend on interleukin 7 (IL-7) for survival. In DN2 and DN3 cells, a new role has now been identified for signaling via the IL-7 receptor and the kinase Jak3 that leads to noncanonical activation of the transcription factor NFATc1 and upregulation of expression of the antiapoptotic protein Bcl-2.

Interleukin 7 (IL-7) signaling is essential during early lymphocyte development. Patra and colleagues identify a distinct IL-7–kinase Jak3–dependent pathway that activates the transcription factor NFATc1 in DN1 thymocytes to promote their survival.

Immune responses can cause immunopathology. Yarovinsky and colleagues show that IFN-γ induced by T cell–intrinsic TLR signaling in CD4⁺ T_H1 cells during Toxoplasma gondii infection causes dysbiosis and loss of Paneth cells.

Why signaling via both the receptor for interleukin 7 (IL-7R) and the T cell antigen receptor (TCR) is required for T cell homeostasis has been unclear. Singer and colleagues show that engagement of the TCR interrupts IL-7R signals to prevent a mechanism of cytokine-induced cell death.

Follicular regulatory T cells control humoral immune responses, but how these cells are in turn controlled has been unclear. Sharpe and colleagues demonstrate that signaling via PD-1 regulates number and function of these cells.

Complement provides costimulatory signals to T cells. Medof and colleagues demonstrate that an absence of complement signaling in naive T cells generates an autoinductive loop to drive induced regulatory T cells.

The intracellular sensor DDX41 is important for generating innate responses to DNA viruses. Liu et al. demonstrate that the ubiquitin ligase TRIM21 degrades and thereby regulates DDX41-dependent responses.

Hacohen and colleagues use an integrative approach that combines quantitative proteomics, genomics and small molecule perturbations to identify new genes involved in DNA sensing and type I interferon production.