Immune Regulation News Volume 5.43 | Nov 8 2013

The Mechanism of Anti-CD20-Mediated B Cell Depletion Revealed by Intravital Imaging
The authors found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, they established that, upon anti-CD20 treatment, Kupffer cells mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. [J Clin Invest] Full Article | Press Release

B Cells Are Critical for Autoimmune Pathology in Scurfy Mice
Scientists showed that B cells and the production of autoantibodies plays a major role for skin, liver, lung, and kidney inflammation and therapeutic depletion of B cells resulted in reduced tissue pathology and in prolonged survival. In contrast, the absence of B cells did not impact systemic T-cell activation and hyperreactivity, indicating that autoantibody production by B cells may be a major factor for the autoimmune pathology in mice deficient for regulatory T cells. [Proc Natl Acad Sci USA] Abstract

Targeting PKC in Human T Cells Using Sotrastaurin (AEB071) Preserves Regulatory T Cells and Prevents IL-17 Production
Scientists showed that sotrastaurin inhibited effector T cell responses, whereas the regulatory response was enhanced. Sotrastaurin prevented TCR/CD28-induced T-cell activation and pro-inflammatory cytokine production, but preserved a stable regulatory T-cells phenotype as evidenced by maintenance of suppressive capacity, high Foxp3 and CD25 expression, and lack of IL-17A and IFNγ production. [J Invest Dermatol] Abstract

Myosin-Primed Tolerogenic Dendritic Cells Ameliorate Experimental Autoimmune Myocarditis
Researchers investigated whether tolerogenic dendritic cell therapy in an experimental autoimmune myocarditis mouse model can suppress inflammatory myocarditis, a potential precursor of dilated cardiomyopathy. [Cardiovasc Res] Abstract

Recipient Myeloid-Derived Immunomodulatory Cells Induce PD-1 Ligand-Dependent Donor CD4⁺Foxp3⁺ Regulatory T Cell Proliferation and Donor-Recipient Immune Tolerance after Murine Nonmyeloablative Bone Marrow Transplantation
The authors showed previously that nonmyeloablative total lymphoid irradiation/rabbit anti-thymocyte serum conditioning facilitates potent donor-recipient immune tolerance following bone marrow transplantation across MHC barriers via recipient invariant NKT cell-derived IL-4-dependent expansion of donor Foxp3⁺ naturally occurring regulatory T cells. They now report a more specific mechanism. [J Immunol] Abstract

Development of Virus-Specific CD4⁺ and CD8⁺ Regulatory T Cells Induced by Human Herpesvirus-6 Infection
Scientists characterized human herpesvirus 6 (HHV-6)-specific T cells in peripheral blood mononuclear cells from HHV-6-infected donors. Their results showed that HHV-6 infection could induce both CD4⁺ and CD8⁺ HHV-6-specific regulatory T cells. [J Virol] Abstract

Prevention of GVHD by Adoptive T Regulatory Therapy Is Associated with Active Repression of Peripheral Blood Toll-Like Receptor-5 mRNA Expression
To investigate potential mechanisms responsible for reduced graft-versus-host disease (GVHD) risk, investigators analyzed peripheral blood mononuclear cell mRNA expression of a tolerance gene set previously identified in operational tolerant kidney transplant recipients, comparing healthy controls to patients who received no natural regulatory T cells (nTregs) or nTregs with and without GVHD. [Biol Blood Marrow Transplant] Abstract

Homogeneous Expansion of Human T-Regulatory Cells via Tumor Necrosis Factor Receptor 2
With the goal of producing homogeneous T-regulatory cells (T_regs), researchers developed a novel expansion protocol targeting tumor necrosis factor receptors (TNFR) on T_regs. In in vitro studies, a TNFR2 agonist was found superior to standard methods in proliferating human T_regs into a phenotypically homogeneous population consisting of 14 cell surface markers. [Sci Rep] Full Article

Immunobiology of Mesenchymal Stem Cells
The authors focus on the crosstalk between mesenchymal stem cells and immune responses and their potential clinical applications, especially in inflammatory diseases. [Cell Death Differ] Full Article

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STEMCELL Technologies Receives Government of Canada Support to Develop New Cell Isolation Technology that Will Enable Advancements in the Study of the Immune Response to HIV and the Development of HIV Vaccines
STEMCELL Technologies announced that the National Research Council of Canada Industrial Research Assistance Program will provide up to $1.5 million in financial support for the development of cell isolation technology that will further basic and translational HIV research as well as broader research in infectious disease. [STEMCELL Technologies Inc.] Press Release

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NEW PhD Studentship – Systems Biology and Lymphocyte Activation (University of Oxford)

Tenure-Track Faculty Position – Women’s Infectious Disease Research (Washington University School of Medicine)

Research Studentship – Imaging Membrane Lipid in Activating T Cells (King’s College London)

Postdoctoral Position – Lymphocyte Motility (INSERM)

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Postdoctoral Fellow – Ripk1 in Innate Immune Responses and Necroptosis (University of Massachusetts Medical School)

PhD/Postdoctoral Positions – Quantitative T-Cell Immunology (University of Leeds)

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

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

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Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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