Immune Regulation News Volume 6.37 | Oct 3 2014

Continuous Requirement for the TCR in Regulatory T Cell Function
Scientists demonstrated that inducible ablation of the T cell antigen receptor (TCR) resulted in T_reg cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of T_reg cell signature genes or altered ability to sense and consume interleukin 2. [Nat Immunol] Abstract

The Same Self-Peptide Selects Conventional and Regulatory ​CD4⁺ T Cells with Identical Antigen Receptors
Researchers show that the binding of identical T-cell receptors (TCRs) to the same ubiquitously expressed MHC/peptide complex often directs thymocytes to both ​CD4⁺ lineages, indicating that the TCR affinity does not play the instructive role, and that restricted presentation of peptides in ‘thymic niches’ is not necessary for selection of ​CD4⁺​Foxp3⁺ T cells. [Nat Commun] Abstract

Tsc1 Promotes the Differentiation of Memory CD8⁺ T Cells via Orchestrating the Transcriptional and Metabolic Programs
Scientists describe that tuberous sclerosis 1 (Tsc1), a regulator of mechanistic target of rapamycin signaling, plays a crucial role in promoting the differentiation and function of memory CD8⁺ T cells in response to Listeria monocytogenes infection. [Proc Natl Acad Sci USA] Abstract

Association of the EF-Hand and PH Domains of the Guanine Nucleotide Exchange Factor SLAT with IP₃ Receptor 1 Promotes Ca²⁺ Signaling in T Cells
Disruption of the SWAP-70-like adaptor of T cells (SLAT)-inositol 1,4,5-trisphosphate (IP₃) receptor type 1 (IP₃R1) interaction with cell-permeable, IP₃R1-based fusion peptides inhibited T cell receptor-stimulated Ca²⁺ signaling, activation of the transcription factor NFAT, and production of cytokines, suggesting that this interaction is required for optimal T cell activation. [Sci Signal] Abstract

Blockade of mTOR Signaling via Rapamycin Combined with Immunotherapy Augments Anti-Glioma Cytotoxic and Memory T Cells’ Functions
Researchers demonstrate that administration of Rapamycin with Fms-like tyrosine kinase 3 ligand + thymidine kinase/ganciclovir immunotherapy enhanced the cytotoxic activity of anti-tumor CD8⁺ T cells. [Mol Cancer Ther] Abstract | Press Release

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity
Researchers used spinning disk confocal microscopy in Foxp3-GFP mice to visualize rolling of endogenous regulatory T cells (Tregs) in dermal postcapillary venules. Tregs underwent consistent but low-frequency rolling interactions under resting and inflamed conditions. [J Immunol] Abstract

Intramuscular Delivery of Heterodimeric IL-15 DNA in Macaques Produces Systemic Levels of Bioactive Cytokine Inducing Proliferation of NK and T Cells
Administration of DNAs expressing heterodimeric interleukin-15 (IL-15) resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8⁺NK cells, all memory CD8⁺ T-cell subsets and effector memory CD4⁺ T cells. [Gene Ther] Full Article

Lung Angiogenesis Requires CD4⁺Foxp3⁺ Regulatory T Cells
In a model of left lung ischemia, an increase in CD4⁺CD25⁺Foxp3⁺ cells was observed three to five days after the onset of ischemia in wild type C57Bl/6 mice. Using transgenic mice where Foxp3⁺ regulatory T cells (Treg) can be depleted with diphtheria toxin, scientists unexpectedly found that Foxp3⁺ Treg depletion led to markedly reduced lung angiogenesis. [Am J Respir Cell Mol Biol] Abstract

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Foundation Responds to Eli Lilly and Company’s Release of Data from Clinical Trial of Tabalumab
The Lupus Foundation of America issued a statement in response to Eli Lilly and Company’s announcement of the results of two Phase III clinical trials of tabalumab, a biologic agent studied for the treatment of lupus. The trials did not show favorable results and the company is terminating these studies. [Lupus Foundation of America, Inc.] Press Release

Horwitz Prize Awarded for Work on Therapy that Uses the Immune System to Destroy Cancer Cells
Columbia University will award the 2014 Louisa Gross Horwitz Prize to James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center, for his work on understanding the process of T-cell activation and for developing therapies that harness the immune system to fight cancer. [Columbia University] Press Release

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