Immune Regulation News Volume 5.03 | Jan 25 2013

Caspase-11 Protects against Bacteria that Escape the Vacuole
Researchers report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) aberrantly enter the cytosol. These mutants triggered caspase-11, which enhanced clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. [Science] Abstract | Press Release

Mutual Expression of the Transcription Factors Runx3 and ThPOK Regulates Intestinal CD4⁺ T Cell Immunity
Although CD4⁺ T cells are crucial for defense, intestinal homeostasis precludes exaggerated responses to luminal contents, whether they are harmful or not. Researchers investigated mechanisms used by CD4⁺ T cells to avoid excessive activation in the intestine. [Nat Immunol] Abstract

Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells
Scientists differentiated mouse induced pluripotent stem cells (iPSCs) into embryoid bodies (EBs) or representative cell types spanning the three embryonic germ layers and assessed their immunogenicity in vitro and after their transplantation into syngeneic recipients. They found no evidence of increased T cell proliferation in vitro, rejection of syngeneic iPSC-derived EBs/tissue-specific cells after transplantation, or an antigen-specific secondary immune response. [Cell Stem Cell] Abstract

Immunoglobulins Drive Terminal Maturation of Splenic Dendritic Cells
The authors show that dendritic cells (DCs) arising in the absence of immunoglobulins (Ig) in vivo are impaired in cross-presentation of soluble antigen. Function of DCs could be restored by transfer of Ig irrespective of antigen specificity and isotype. [Proc Natl Acad Sci USA] Abstract | Press Release

Uracil DNA Glycosylase Initiates Degradation of HIV-1 cDNA Containing Misincorporated dUTP and Prevents Viral Integration
Uracilation of invading retroviral DNA is thought to be an innate immunity barrier to retroviral infection, but the mechanistic features of this immune pathway and the cellular fate of uracilated retroviral DNA products is not known. Here researchers developed a model system in which the cellular dUTP:dTTP ratio can be pharmacologically increased to favor dUTP incorporation, allowing dissection of this innate immunity pathway. [Proc Natl Acad Sci USA] Abstract | Press Release

Human CD8⁺ Regulatory T Cells Inhibit GvHD and Preserve General Immunity in Humanized Mice
Investigators successfully generated human alloantigen-specific CD8^hi regulatory T cells (T_regs) in a large scale from antigenically naïve precursors ex vivo using allogeneic CD40-activated B cells as stimulators. They demonstrated that ex vivo-induced CD8^hi T_regs controlled graft-versus-host disease (GvHD) in an allospecific manner by reducing alloreactive T cell proliferation as well as decreasing inflammatory cytokine and chemokine secretion within target organs through a CTLA-4-dependent mechanism in humanized mice. [Sci Transl Med] Abstract

Differential Ly49e Expression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells
Among the entire Ly49 receptor family, Ly49E is the only Ly49 member expressed by epidermal-localized γδ T cells and their fetal thymic TCRγδ precursors, and it is the most abundantly expressed member on intestinal intraepithelial γδ T cell lymphocytes. Researchers provide mechanistic insights into the regulation of Ly49e expression in γδ T cells. [J Immunol] Abstract

Temporal Dynamics of the Primary Human T Cell Response to Yellow Fever Virus 17D as It Matures from an Effector- to a Memory-Type Response
Scientists studied the temporal dynamics, composition, and character of the primary human T cell response to yellow fever virus. [J Immunol] Abstract

Myeloid Dendritic Cells (DCs) of Susceptible Mice to Paracoccidioidomycosis Suppress T Cell Responses whereas Myeloid and Plasmacytoid DCs from Resistant Mice Induce Effector and Regulatory T Cells
The early host response to Paracoccidioides brasiliensis infection is not known since the disease is diagnosed at later phases of infection. The authors aimed to characterize the influence of dendritic cells in the innate and adaptive immunity of susceptible and resistant mice. [Infect Immun] Abstract

PGE₂ Differentially Regulates Monocyte-Derived Dendritic Cell Cytokine Responses Depending on Receptor Usage (EP₂/EP₄)
Researchers found that irrespective of the human donor, monocyte-derived dendritic cells (MoDCs) express three of the four prostaglandin E₂ (PGE₂) receptor subtypes (EP_2-4), although only EP₂ and EP₄ were active with respect to cytokine production. Using selective EP receptor antagonists and agonists, they demonstrated that PGE₂ coordinates control of IL-23 release in a dose-dependent manner by differential use of EP₂ and EP₄ receptors in LPS-activated MoDCs. [Mol Immunol] Abstract

NeoStem’s Subsidiary, Progenitor Cell Therapy, Enters into a Cell Therapy Manufacturing Services Agreement with Adaptimmune
NeoStem, Inc. and its subsidiary, Progenitor Cell Therapy LLC (PCT), together with Adaptimmune Limited and Adaptimmune LLC (Adaptimmune), announced a Services Agreement under which PCT will provide services to support Adaptimmune’s NYESO-1^c259-T cell therapy product being developed for multiple oncology indications. [NeoStem, Inc.] Press Release

AACR and CRI Announce Lloyd J. Old Award in Cancer Immunology
The American Association for Cancer Research (AACR) and the Cancer Research Institute (CRI) have collaborated to establish a new award to honor the memory of the late Lloyd J. Old, M.D., a scientist whose lifetime of outstanding and innovative research in cancer immunology, as well as his decades of leadership in fostering the field, has had a far-reaching impact on cancer. [American Association for Cancer Research] Press Release

Quest PharmaTech Enrolls 40th Patient in Its Phase II Oregovomab Front-Line Chemo-Immunotherapy Clinical Trial for Ovarian Cancer in Italy and the U.S.
Quest PharmaTech Inc. announced that it has achieved 50% accrual having enrolled the 40^th patient in its ongoing 80 patient Phase II Oregovomab front-line chemo-immunotherapy clinical trial in Italy and the U.S. [PR Newswire Association LLC] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Cold Spring Harbor Asia Conferences: Mechanisms and Functions of Non-Apoptotic Cell Death
April 15-19, 2013
Suzhou, China

NEW 11th Cancer Immunotherapy (CIMT) Annual Meeting 
May 14-16, 2013
Mainz, Germany

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Postdoctoral Position – Immune Regulation (Trinity College Dublin)

Associate Scientist – Clinical Immunology (Crucell Holland B.V.)

Postdoctoral Fellow – Transcriptional Regulation in CD8 T Lymphocytes (Université Libre de Bruxelles – Institute for Medical Immunology)

Postdoctoral Fellow (Medical University of Warsaw)

Faculty Positions – Cancer Inflammation and Tolerance (Georgia Health Sciences University Cancer Center)

PhD Studentship/Postdoctoral Positions – Tumor Immunology and Cancer Stem Cell Research (University Clinics Freiburg)

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

Postdoctoral Position – IL-17 and Inflammation Research (Hospices Civils de Lyon)

PhD Position – Mast Cells in HPV-Induced Skin Cancer (TU Dresden – Institute of Immunology)

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