Immune Regulation News Volume 5.37 | Sep 27 2013

CD301b⁺ Dermal Dendritic Cells Drive T Helper 2 Cell-Mediated Immunity
By using an in vivo depletion approach, scientists have shown that dendritic cells expressing CD301b were required for the generation of T helper cells after subcutaneous immunization with ovalbumin along with papain or alum. [Immunity] Abstract | Graphical Abstract

Transforming Growth Factor-β Signaling Controls the Formation and Maintenance of Gut-Resident Memory T Cells by Regulating Migration and Retention
Investigators showed that transforming growth factor-β (TGF-β) controlled both stages of gut tissue-resident memory T (Trm) cell differentiation through different mechanisms. During the formation phase of Trm cells, TGF-β signaling inhibited the migration of effector CD8⁺ T cells from the spleen to the gut by dampening the expression of integrin α4β7. [Immunity] Abstract | Graphical Abstract

Alveolar Macrophages Develop from Fetal Monocytes that Differentiate into Long-Lived Cells in the First Week of Life via GM-CSF
By performing BrdU labeling and parabiosis experiments in adult mice, scientists found that circulating monocytes contributed minimally to the steady-state alveolar macrophages pool. [J Exp Med] Abstract

Dendritic Epidermal T Cells Regulate Skin Antimicrobial Barrier Function
The authors determined that TCR stimulation and skin injury induces IL-17A production by a subset of dendritic epidermal T cells (DETC). This subset of IL-17A-producing DETC was distinct from IFN-γ producers, despite similar surface marker profiles. Functionally, blocking IL-17A or genetic deletion of IL-17A resulted in delayed wound closure in animals. [J Clin Invest] Full Article | Press Release

Generation of Effector Memory T Cell-Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination
The authors describe a pulmonary vaccination strategy combining Toll-like receptor agonists with antigen-carrying lipid nanocapsules, which elicit high-frequency, long-lived, antigen-specific effector memory T cell responses at multiple mucosal sites. [Sci Transl Med] Abstract

A Novel Subset of Helper T Cells Promotes Immune Responses by Secreting GM-CSF
By depleting major cytokines during the differentiation of CD4⁺ T cells in vitro, researchers derived cells that were found to produce large amounts of granulocyte macrophage-colony-stimulating factor (GM-CSF), but little of the cytokines produced by other helper T subsets. [Cell Death Differ] Abstract

CD4 Blockade Directly Inhibits Mouse and Human CD4⁺ T Cell Functions Independent of Foxp3⁺ Tregs
Utilizing mixed leukocyte reactions reflecting physiological interactions between T cells and dendritic cells, researchers report that anti-CD4 treatment inhibits CD4⁺Foxp3^– T cell proliferation in an IL-2-independent fashion. Notably, YTS177.9 binding induces a rapid internalization of CD4 on both CD4⁺Foxp3^– T cells and Foxp3⁺ regulatory T cells (Tregs). [J Autoimmun] Abstract

Highly Prevalent Colorectal Cancer-Infiltrating LAP⁺ Foxp3^– T Cells Exhibit More Potent Immunosuppressive Activity than Foxp3⁺ Regulatory T Cells
Flow cytometry revealed that the majority of intratumoral CD4⁺Foxp3⁺ T cells (Tregs) were Helios⁺ and expressed higher levels of cytotoxic T-lymphocyte antigen 4 and CD39 than Tregs from colon and blood. Moreover, ~30% of intratumoral CD4⁺Foxp3^– T cells expressed markers associated with regulatory functions, including latency-associated peptide, lymphocyte activation gene-3, and CD25. [Mucosal Immunol]
Full Article

The Skin-Resident and Migratory Immune System in Steady State and Memory: Innate Lymphocytes, Dendritic Cells and T Cells
The authors outline many of the innate and adaptive immune cell types associated with the skin, focusing on the steady state in mice and men, and include a broad update of dendritic cell function and T cell surveillance. [Nat Immunol] Abstract

Location and Cellular Stages of Natural Killer Cell Development
Gaining a better understanding of the processes that govern natural killer (NK) cell development should allow researchers to harness better NK cell functions in multiple clinical settings, as well as to gain further insight into how these cells undergo malignant transformation. In this review, the authors summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. [Trends Immunol] Abstract

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Etubics Awarded $1.5 Million Manufacturing Contract for Breast Cancer Immunotherapeutic
Etubics Corporation announced that it has received a contract of approximately $1.5 million from Small Business Innovation Research Development Center of the National Cancer Institute to manufacture Etubics’ breast cancer immunotherapeutic, ETBX-021. ETBX-021 utilizes the Etubics Platform, which is stealth to the immune system and has the ability to deliver a long lasting “active” immune response against cancer targets, educating the immune system’s T-cells to act as if the cancer was a simple virus. [Etubics Corporation] Press Release

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