Increased internalization of Staphylococcus aureus and cytokine expression in human Wharton's jelly mesenchymal stem cells.

Background: Although a large number of studies have documented the interaction of mesenchymal stem cells (MSCs) with cells of both the innate and adaptive immune systems, not much is known about how bacteria interact with MSCs and how this might influence MSCs behavior. In this study, we investigated the impact of Staphylococcus aureus (S. aureus), on viability and cytokines' production of human Wharton's jelly-MSCs (WJ-MSCs).

Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease.

Background & Aims: New therapeutic strategies are needed for patients with refractory Crohn's disease (CD). We evaluated data from the Crohn's And Treg Cells Study (CATS1) to determine the safety and efficacy of antigen-specific T-regulatory (Treg) cells for treatment of patients with refractory CD.

Methods: We performed a 12-week, open-label, multicenter, single-injection, escalating-dose, phase 1/2a clinical study in 20 patients with refractory CD.

Isolation of functional autologous collagen-II specific IL-10 producing Tr1 cell clones from rheumatoid arthritis blood.

IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4+ regulatory cells able to prevent in vitro bystander T-cell proliferation and to inhibit a wide range of inflammatory diseases in mice. Our aim was to evaluate the frequency and function of joint specific Tr1 cells in the peripheral blood of severe Rheumatoid Arthritis (RA) patients. The collagen II protein was chosen to isolate Tr1 cells specific for a joint antigen.

Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases.

IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4(+) regulatory cells able to prevent in vitro bystander T-cell proliferation and to cure ongoing chronic colitis in mice. In order to assess the efficacy and tolerance of Tr1 cell therapy in a Phase I/IIa clinical trial in patients displaying severe Crohn's disease, we set up a reproducible manufacturing process for the GMP production of human ovalbumin specific Tr1 cells. Procedures used for Tr1-cell production include the use of Drosophila derived artificial Antigen Presenting Cells transfected with specific stimulatory molecules.

Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes.

Background & Aims: Saccharomyces boulardii is a nonpathogenic yeast used for treatment of diarrhea. We used a mice model of inflammatory bowel disease (IBD) to analyze the effects of S boulardii on inflammation.

Methods: Lymphocyte-transferred SCID mice, displaying IBD, were fed daily with S boulardii.

In vivo follow-up of rat tumor models with 2-deoxy-2-[F-18]fluoro-D-glucose/dual-head coincidence gamma camera imaging.

Unlabelled: Before studying the impact of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) imaging with a dual-head coincidence gamma camera (DHC) for the follow-up of animal tumor models, we wanted to optimize this technique.

Methods: Three different animal tumor models (osteosarcoma, melanoma, and breast cancer) were studied after FDG injection. Dynamic and dual time point FDG/DHC imaging were studied from one hour to five hours postinjection.

Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice.

Background: Atherosclerosis is an immunoinflammatory disease. Here we examined the role of leukocyte-derived interleukin 10 (IL-10) on advanced atherosclerosis development in low-density lipoprotein receptor knockout (LDLr-/-) mice.

Methods And Results: Bone marrow cells harvested from C57BL/6 IL-10-/- and IL-10+/+ mice were transplanted into irradiated male LDLr-/- mice.

Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition.

Background: Bone marrow-derived mononuclear cells (BM-MNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. We evaluated the safety of BM-MNC-based therapy in the setting of atherosclerosis.

Methods And Results: Apolipoprotein E (apoE)-knockout (KO) mice were divided into 4 groups: 20 nonischemic mice receiving intravenous injection of either saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) and 20 mice with arterial femoral ligature receiving intravenous injection of either saline (n=10) or 10(6) BM-MNCs from wild-type animals (n=10) at the time of ischemia induction.

A comparative study between T regulatory type 1 and CD4+CD25+ T cells in the control of inflammation.

There is now compelling evidence that CD4(+)CD25(+) T cells play a major role in the maintenance of tolerance. Besides CD4(+)CD25(+) T cells, different populations of regulatory CD4(+) T cells secreting high amounts of IL-10 (T regulatory type 1 (Tr1)) or TGF-beta (Th3) have also been described in in vivo models. In the lymphocyte transfer model of inflammatory bowel disease, we show here that the control of inflammation during the first weeks is not due to a complete inhibition of differentiation of aggressive proinflammatory T cells, but is the result of a balance between proinflammatory and Tr cells.

Rho-associated protein kinase contributes to early atherosclerotic lesion formation in mice.

Members of the Rho family of small GTPases have been recently implicated in inflammatory signaling. We examined the effect of in vivo inhibition of Rho kinase on atherogenesis in mice. Low-density lipoprotein receptor (LDLR) knockout (KO) mice fed a cholate-free high-fat diet received daily intraperitoneal injection of saline (n=8, control group) or Y-27632 (30 mg/kg, n=9), a specific Rho kinase inhibitor.

Specific abrogation of transforming growth factor-beta signaling in T cells alters atherosclerotic lesion size and composition in mice.

A large body of evidence supports a role for proinflammatory mediators in atherosclerotic disease progression and instability. However, only few endogenous mechanisms have been suggested that could alter disease progression. One such mechanism is thought to be mediated by transforming growth factor beta (TGF-beta).

Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice.

Background: T helper type 1 (Th1) response plays a permissive role in atherosclerosis. We hypothesized that adoptive transfer of a novel subtype of T lymphocytes called regulatory T cells type 1 (Tr1) would inhibit Th1 responses by inducing a bystander immune suppression and therefore limit the development of atherosclerosis.

Methods And Results: Clones of ovalbumin (OVA)-specific Tr1 cells expanded in vitro were administered intraperitoneally (106 cells per mouse) with their cognate antigen (50 microg of OVA subcutaneously in complete Freund's adjuvant [CFA]) to female apolipoprotein E-knockout mice.

Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo.

Active suppression is mediated by a subpopulation of CD4(+) T cells that prevents autoimmunity. However, the mechanisms involved in their differentiation in vivo are currently under intensive research. Here we show that in vitro culture of bone marrow cells in the presence of IL-10 induces the differentiation of a distinct subset of dendritic cells with a specific expression of CD45RB.

Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation.

The physiologic role of the mu opioid receptor (MOR) in gut nociception, motility, and secretion is well established. To evaluate whether MOR may also be involved in controlling gut inflammation, we first showed that subcutaneous administration of selective peripheral MOR agonists, named DALDA and DAMGO, significantly reduces inflammation in two experimental models of colitis induced by administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) or peripheral expansion of CD4(+) T cells in mice. This therapeutic effect was almost completely abolished by concomitant administration of the opioid antagonist naloxone.