Immune Regulation News Volume 5.10 | Mar 15 2013

The Transcription Factor T-bet Is Essential for the Development of NKp46⁺ Innate Lymphocytes via the Notch Pathway
The authors report that the transcription factor T-bet (encoded by Tbx21) is essential for the development of NKp46⁺ innate lymphoid cells (ILCs) but not of lymphoid tissue-inducer cells or nuocytes. Deficiency in interleukin 22-producing NKp46⁺ ILCs resulted in greater susceptibility of Tbx21^−/− mice to intestinal infection. [Nat Immunol] Abstract | Press Release

Inadequate T Follicular Cell Help Impairs B Cell Immunity during HIV Infection
Researchers report that even though there is an expansion of follicular helper T (T_FH) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. They found a higher frequency of programmed cell death ligand 1 (PD-L1)⁺ germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1–PD-L1 interaction in regulating T_FH cell function. [Nat Med] Abstract

Persistent Antigen at Vaccination Sites Induces Tumor-Specific CD8⁺ T Cell Sequestration, Dysfunction and Deletion
To understand why cancer vaccine-induced T cells often do not eradicate tumors, investigators studied immune responses in mice vaccinated with gp100 melanoma peptide in incomplete Freund’s adjuvant, which is commonly used in clinical cancer vaccine trials. [Nat Med] Abstract | Press Release | Video

Signals via the Adaptor MyD88 in B Cells and Dendritic Cells Make Distinct and Synergistic Contributions to Immune Activation and Tissue Damage in Lupus
Investigators demonstrated that formation of anti-nuclear antibodies in MRL.Fas^lpr mice entirely depends on the Toll-like receptor (TLR) signaling adaptor MyD88 in B cells. Further, MyD88 deficiency in B cells ameliorated nephritis, including antibody-independent interstitial T cell infiltrates, suggesting that nucleic acid-specific B cells activate nephrotoxic T cells. [Immunity] Abstract

IL-1R1 Is Required for Dendritic Cell-Mediated T Cell Reactivation within the CNS during West Nile Virus Encephalitis
Scientists found that IL-1R1 is critical for effector T cell reactivation and limits inflammation within the central nervous system (CNS) during murine West Nile virus (WNV) encephalitis. Ex vivo analysis of CD4⁺ T cells from WNV-infected CNS of IL-1R1^−/− mice revealed impaired effector responses, whereas CD8⁺ T cells revealed no cell intrinsic defects in response to WNV antigen. [J Exp Med] Abstract

Rapamycin-Treated Human Endothelial Cells Preferentially Activate Allogeneic Regulatory T Cells
The authors report the effects of rapamycin on endothelial cell (EC) alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. [J Clin Invest] Full Article

B Cells Promote Inflammation in Obesity and Type 2 Diabetes through Regulation of T-Cell Function and an Inflammatory Cytokine Profile
Investigators demonstrated that B cells from type 2 diabetes (T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. [Proc Natl Acad Sci USA] Abstract | Press Release

Targeting the Intracellular WT1 Oncogene Product with a Therapeutic Human Antibody
Using phage display technology, the authors discovered a fully human “T cell receptor-like” monoclonal antibody, ESK1, specific for the Wilms tumor 1 (WT1) RMFPNAPYL peptide/human leukocyte antigen (HLA)-A0201 complex. ESK1 bound to several leukemia and solid tumor cell lines and primary leukemia cells, in a WT1- and HLA-A0201-restricted manner, with high avidity. ESK1 mediated antibody-dependent human effector cell cytotoxicity in vitro. [Sci Trans Med] Abstract | Press Release

Dendritic Cell Immune Receptor (DCIR) Regulates Chikungunya Virus Pathogenesis in Mice
Alphaviruses are known to interact with members of the C-type lectin receptor family of pattern recognition proteins, and given that the DCIR is known to act as a negative regulator of the host inflammatory response and has previously been associated with rheumatoid arthritis, the authors evaluated DCIR’s role in response to Chikungunya virus infection. [J Virol] Abstract

New AAN/ALS Association Clinical Fellow Will Pursue Immune Biomarkers
The ALS Association and the American Academy of Neurology (AAN) announced that James Berry, M.D. is this year’s recipient for the Richard Olney AAN/ALS Association Clinician Scientist Development Award, which is a part of The Association’s research program Translational Research Advancing Therapy for Amyotrophic Lateral Sclerosis (ALS). For his Fellowship research, Dr. Berry will lead a longitudinal study to characterize immune system changes that may be used as a biomarker in ALS. [The ALS Association] Press Release

Receptos Licenses Anti-Interleukin-13 Antibody from AbbVie for Phase II Development in Orphan Disease
Receptos Inc. announced that it has entered a Development License and Option Agreement to in-license a humanized anti-interleukin-13 antibody asset from AbbVie. The asset, designated RPC4046 by Receptos, has completed a first-in-human Phase I study. Under the agreement, Receptos will conduct a Phase II clinical study to demonstrate proof-of-concept in eosinophilic esophagitis, an indication designated as an Orphan Disease by the United States FDA. [Receptos, Inc.] 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)

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

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

PhD Candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – NK/T Cells (The Ohio State University – Comprehensive Cancer Center)

Postdoctoral Position – Immunology (Institut Pasteur)

Postdoctoral Fellow – Immunotherapeutics in Childhood Cancer (Perelman School of Medicine at the University of Pennsylvania)

Postdoctoral Position – Type 1 Diabetes and Systemic Lupus Erythematosus (University of Florida)

PhD Student/ Early Stage Researcher – T Cell Regulation (The Netherlands Cancer Institute [NKI-AvL])

PhD Studentship – Thymic Dendritic Cells and Regulation of T-Cell Development (University of Birmingham / MRC Centre for Immune Regulation)

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