Immune Regulation News Volume 6.06 | Feb 21 2014

T Cell Repertoire following Autologous Stem Cell Transplantation for Multiple Sclerosis
In a Phase II study of hematopoietic stem cell transplantation (HSCT) for poor-prognosis multiple sclerosis, scientists used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. They found that HSCT has distinctive effects on CD4⁺ and CD8⁺ T cell repertoires. [J Clin Invest]
Full Article | Press Release

Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
Investigators report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia that they treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. [Sci Transl Med] Abstract | Press Release

Targeted Depletion of an MDSC Subset Unmasks Pancreatic Ductal Adenocarcinoma to Adaptive Immunity
The authors showed that selective depletion of one subset of myeloid-derived suppressor cells (MDSC) in an autochthonous, genetically engineered mouse model of pancreatic ductal adenocarcinoma unmasks the ability of the adaptive immune response to engage and target tumor epithelial cells. [Gut] Abstract | Press Release

Prolactin Mediates Psychological Stress-Induced Dysfunction of Regulatory T Cells to Facilitate Intestinal Inflammation
The authors aimed to elucidate a pathological pathway between psychological stress and the dysfunction of regulatory T cells, and its effect on facilitating intestinal inflammation. [Gut] Abstract

Opposing Actions of IL-2 and IL-21 on Th9 Differentiation Correlate with Their Differential Regulation of BCL6 Expression
Researchers show that interleukin 2 (IL-2)-JAK3-STAT5 signaling is required for T-helper 9 (Th9) differentiation, with critical STAT5 binding sites in the gene encoding IL-9 promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and overexpression of BCL6 impaired Th9 differentiation. [Proc Natl Acad Sci USA] Abstract

NF-κB Signaling Mediates Homeostatic Maturation of New T Cells
Investigators identified a role for the Nuclear Factor κ-B (NF-κB) signaling pathway in controlling expression of IL-7 receptor α (IL-7Rα) in new T cells. Perturbations to NF-κB signaling, either by deletion of Inhibitor of Kappa-B Kinase-2 or by inhibiting Rel dimer activity, prevented normal IL-7Rα expression in new T cells. [Proc Natl Acad Sci USA] Abstract

Targeting Sirtuin-1 Alleviates Experimental Autoimmune Colitis by Induction of Foxp3⁺ T-Regulatory Cells
Scientists adoptively transferred CD4⁺CD25^–Foxp3^– T effector (TE) cells from wild-type (WT) or fl-Sirt1/CD4cre mice into B6/Rag1^−/− mice and monitored the mice until they lost 10-15% of their weight. Adoptive transfer of TE cells lacking sirtuin-1 (Sirt1) to B6/Rag1^−/− mice resulted in a 2.8-fold increase in induced Forkhead box P3-positive (Foxp3⁺) T-regulatory cells formation compared with mice receiving WT TE cells and correlated with attenuated colitis and reduced weight loss. [Mucosal Immunol] Abstract

Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization
There are two major suppressor macrophage (MΦ) subsets (M1 and M2 MΦs) that are phenotypically and functionally different. Researchers examined which of the MΦ subsets the mycobacterial infection-induced suppressor MΦs (MIS-MΦs) belong to. MIS-MΦs down-regulated T cell production of Th1 and Th2 cytokines but markedly increased production of interleukin (IL)-17A and IL-22 through up-regulation of Th17 cell expansion. [Sci Rep] Full Article

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Novartis Expands Cancer Immunotherapy Research Program with Acquisition of CoStim
Novartis announced that it is broadening its cancer immunotherapy research program with the acquisition of CoStim Pharmaceuticals Inc., a privately held biotechnology company focused on harnessing the immune system to eliminate immune-blocking signals from cancer. [Novartis AG] Press Release

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NEW Assistant/Associate Professors – Allergic Inflammation and Sensory Neurobiology (North Carolina State University College of Veterinary Medicine)

PhD Student Position – Molecular Immunology (Institute for Research in Biomedicine)

Principal Investigator – Inflammation Research (Northwestern University)

Assistant Professor – Development of Novel Biologicals for Immune-Based Disorders (Leiden Academic Centre For Drug Research)

Postdoctoral Position – Cell Signaling in the Immune System (Baylor Institute for Immunology Research)

Immunology Research Associate Position (Shanghai Jiaotong University School of Medicine)

Postdoctoral Position – Epigenetic Regulation of Interleukin-12 Family Members (Université Libre de Bruxelles)

PhD Position – Biology/Immunology (Saarland University)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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