TlR expression profile of human gingival margin-derived stem progenitor cells

Background: Gingival margin-derived stem/progenitor cells (G-MSCs) show remarkable periodontal regenerative potential in vivo. During regeneration, G-MSCs may interact with their inflammatory environment via toll-likereceptors (TLRs). The present study aimed to depict the G-MSCs TLRs expression profile. Material and Methods: Cells were isolated from free gingival margins, STRO-1-immunomagnetically sorted and seeded to obtain single colony forming units (CFUs). G-MSCs were characterized for CD14, CD34, CD45, CD73, CD90, CD105, CD146 and STRO-1 expression, and for multilineage differentiation potential. Following G-MSCs’ incubation in basic or inflammatory medium (IL-1β, IFN-γ, IFN-α, TNF-α) a TLR expression profile was generated. Results: G-MSCs showed all stem/progenitor cells’ characteristics. In basic medium G-MSCs expressed TLRs 1, 2, 3, 4, 5, 6, 7, and 10. The inflammatory medium significantly up-regulated TLRs 1, 2, 4, 5, 7 and 10 and diminished TLR 6 (p≤0.05, Wilcoxon-Signed-Ranks-Test). Conclusions: The current study describes for the first time the distinctive TLRs expression profile of G-MSCs under uninflamed and inflamed conditions

Time-resolved in situ studies on the formation mechanism of iron oxide nanoparticles using combined fast-XANES and SAXS

The reaction of iron chlorides with an alkaline reagent is one of the most prominent methods for the synthesis of iron oxide nanoparticles. We studied the particle formation mechanism using triethanolamine as reactant and stabilizing agent. In situ fast-X-ray absorption near edge spectroscopy and small-angle X-ray scattering provide information on the oxidation state and the structural information at the same time. In situ data were complemented by ex situ transmission electron microscopy, wide-angle X-ray scattering and Raman analysis of the formed nanoparticles. The formation of maghemite nanoparticles (gamma-Fe2O3) from ferric and ferrous chloride was investigated. Prior to the formation of these nanoparticles, the formation and conversion of intermediate phases (akaganeite, iron(II, III) hydroxides) was observed which undergoes a morphological and structural collapse. The thus formed small magnetite nanoparticles (Fe3O4) grow further and convert to maghemite with increasing reaction time

The Vγ4/butyrophilin conspiracy: novel role of intraepithelial γδ T cells in chronic inflammatory bowel disease

In a recent article published in Science, Dart and colleagues reported that colonic T cells expressing the V γ 4 T-cell receptor (TCR) interact with epithelial butyrophilin-like (BTNL) proteins BTNL3 and BTNL8 in healthy individuals, and they observed a depletion of V γ 4 T cells in in fl ammatory bowel diseases with renormalization associated with disease remission. This paper identifies the BTNL/V γ 4 axis as a new disease modifier in IBD

Gamma Delta T Cells (γδ T Cells) in Health and Disease: In Memory of Professor Wendy Havran

Gamma delta (γδ) T cells are a small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues [...]

Human γδ T lymphocytes for immunotherapeutic strategies against cancer

γδ T lymphocytes are a numerically small subset of T cells with potent cytotoxic activity against a variety of tumor cells. Human γδ T cells expressing the Vγ9Vδ2 T cell antigen receptor recognize endogenous pyrophosphate molecules that are overproduced in transformed cells. Moreover, the intracellular accumulation of such pyrophosphates is strongly enhanced by aminobisphosphonates used in the treatment of osteoporosis and bone metastasis in certain cancer patients. A new concept of cancer immunotherapy is based on the endogenous activation of γδ T cells with aminobisphosphonates plus low-dose interleukin-2

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM. In this respect, we focus on the role of the NKG2D receptor/ligand system. NKG2D ligands are frequently expressed on GBM tumour cells and can activate NKG2D-expressing killer cells including NK cells and γδ T cells. Soluble NKG2D ligands, however, contribute to tumour escape from immunological attack. We also discuss the current immunotherapeutic strategies to improve the survival of GBM patients. Such approaches include the modulation of the NKG2D receptor/ligand system, the application of checkpoint inhibitors, the adoptive transfer of ex vivo expanded and/or modified immune cells or the application of antibodies and antibody constructs to target cytotoxic effector cells in vivo. In view of the multitude of pursued strategies, there is hope for improved overall survival of GBM patients in the future

Tumor-Infiltrating γδ T Cells Suppress T and Dendritic Cell Function via Mechanisms Controlled by a Unique Toll-like Receptor Signaling Pathway

Summaryγδ T cells are important contributors to innate immunity against cancer, but their regulatory role in controlling immune responses remains largely unknown. Here we report that a dominant γδ1 T cell population among lymphocytes infiltrating breast tumors possessed a potent ability to suppress naive and effector T cell responses and to block the maturation and function of dendritic cells. Adoptive cotransfer experiments demonstrated their in vivo suppressive activity. However, their immunosuppressive activity could be reversed by human Toll-like receptor (TLR) 8 ligands both in vitro and in vivo. siRNA-mediated knockdown experiments revealed that MyD88, TRAF6, IKKα IKKβ, and p38α molecules in γδ1 cells were required for these cells to respond to TLR8 ligands, whereas TAK1, JNK, and ERK molecules did not appear to be involved in functional regulation. These results provide new insights into the regulatory mechanisms of tumor-specific γδ T cells and identify a unique TLR8 signaling pathway linking to their functional regulation

Editorial: "Recent Advances in Gamma/Delta T Cell Biology: New Ligands, New Functions, and New Translational Perspectives"

Since their discovery in the mid-1980s, interest in the immunological significance of γδ T cells has been subject to oscillations. The initial excitement over the unexpected discovery of a second T cell receptor (TCR) was followed by years of uncertainty as to the biological importance of these ambivalent T cells. Major breakthroughs led to the identification of specific and unique antigens for the γδ TCR and accumulating evidence now shows that γδ T cells play a major role in local immunosurveillance, thereby controlling tumorigenesis. Since 2004, biannual international γδ T cell conferences are held to bring together experts in basic and clinical γδ T cell research. To make accessible and synthesize the body of knowledge that has been put together, to date, we have organized a “Research Topic” on γδ T cells consisting of a collection of original articles and focused reviews written by leading experts in the field. The idea of this Research Focus was to present the current status and “hot topics” as well as clinical perspectives on γδ T cell research

Vitamin C and Vitamin D-friends or foes in modulating γδ T-cell differentiation?

The differentiation and functional plasticity of T cells are transcriptionally and epigenetically regulated by signals imposed by the local cytokine milieu and a variety of additional factors, including vitamins. Vitamin C has pleiotropic functions in the immune system. It exerts antioxidant activity, can directly kill selected tumor targets, promotes early T-cell differentiation, and enhances Th1 cytokine production in mature T cells

Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells

Surfactant Protein D (SP-D) is an integral molecule of the innate immunity secreted by the epithelial cells lining the mucosal surfaces. Its C-type lectin domain offers pattern recognition functions while it binds to putative receptors on immune cells to modify cellular functions. Activated PBMCs and increased serum levels of SP-D are observed under a range of pathophysiological conditions including infections. Thus, we speculated if SP-D can modulate systemic immune response via direct interaction with activated PBMCs. Here, we have examined interaction of a recombinant fragment of human SP-D (rhSP-D) on PHA-activated PBMCs. We observed a significant downregulation of TLR2, TLR4, CD11c and CD69 upon rhSP-D treatment. rhSP-D inhibited production of Th1 (TNF-α and IFN-γ) and Th17 (IL-17) cytokines along with IL-6. Interestingly, levels of IL-2, Th2 (IL-4) and regulatory (IL-10 and TGF-β) cytokines were unaltered. Differential expression of co-stimulatory CD28 and co-inhibitory CTLA4 expression along with their ligands CD80 and CD86 revealed selective up-regulation of CTLA4 at both mRNA and protein level. In addition, rhSP-D induced apoptosis only in the activated but not in non-activated PBMCs. Blockade of CTLA4 inhibited rhSP-D mediated apoptosis, confirming an involvement of CTLA4 in induction of apoptosis. We conclude that SP-D restores immune homeostasis: it regulates expression of immunomodulatory receptors and cytokines, which is followed by apoptosis induction of immune-activated cells. These findings appear to suggest a general role for SPD in immune surveillance against activated immune cells