Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1–Associated Neurologic Disease

ObjectiveTo test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP).MethodsPBMCs from patients with HAM/TSP were cultured in the presence and absence of teriflunomide and assessed for cell viability, lymphocyte proliferation, activation markers, HTLV-1 tax and HTLV-1 hbz messenger ribonucleic acid (mRNA) expression, and HTLV-1 Tax protein expression.ResultsIn culture, teriflunomide did not affect cell viability. A concentration-dependent reduction in spontaneous proliferation of PBMCs was observed with 25 μM (38.3% inhibition), 50 μM (65.8% inhibition), and 100 μM (90.7% inhibition) teriflunomide. The inhibitory effects of teriflunomide were detected in both CD8+ and CD4+ T-cell subsets, which are involved in the immune response to HTLV-1 infection and the pathogenesis of HAM/TSP. There was no significant change in HTLV-1 proviral load (PVL) or tax mRNA/Tax protein expression in these short-term cultures, but there was a significant reduction of HTLV-1 PVL due to inhibition of proliferation of CD4+ T cells obtained from a subset of patients with HAM/TSP.ConclusionsThese results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection and may have potential as a therapeutic option in patients with HAM/TSP.

EFFECT OF FDT WITH CHLORINE E 6 (X- E 6) ON VIABILITY AND FUNCTIONAL ACTIVITY OF PERIPHERAL BLOOD’S LYMPHOCYTES

We expiremented with mice inoculated with intramuscularly embryocarcinoma and registered functional condition of T-lymphocytic link of cells of bone brain and spleen to the index of spontaneous and stimulated by mitogen (PHA) proliferation. Intact animals and the ones which we introduced with Chlorine e6 and keep in dark conditions have revealed the zero level of the indexes. But the animals being introduced with Chlorine e6 and activated with laser and light-emitting diode radiation have been notable for the index of mitogen (PHA) stimulation. It was established to 25% with the index of spontaneous proliferation remained on zero mark. Animals with embryocarcinoma after FDT with X-e6 with or without glycosamine show immunostimulating effect.

Profibrotic function of pulmonary group 2 innate lymphoid cells is controlled by Regnase-1

Regnase-1 is an RNase critical for posttranscriptional control of pulmonary immune homeostasis in mice by degrading immune-related mRNAs. However, little is known about the cell types Regnase-1 controls in the lung, and its relevance to human pulmonary diseases.Regnase-1-dependent changes in lung immune cell types were examined by a competitive bone marrow transfer mouse model, and group 2 innate lymphoid cells (ILC2s) were identified. Then the associations between Regnase-1 in ILC2s and human diseases were investigated by transcriptome analysis and a bleomycin-induced pulmonary fibrosis mouse model. The clinical significance of Regnase-1 in ILC2s was further assessed using patients-derived cells.Regnase-1-deficiency resulted in the spontaneous proliferation and activation of ILC2s in the lung. Intriguingly, genes associated with pulmonary fibrosis were highly upregulated in Regnase1-deficient ILC2s compared with wild-type, and supplementation of Regnase-1-deficient ILC2s augmented bleomycin-induced pulmonary fibrosis in mice. Regnase-1 suppresses mRNAs encoding transcription factors Gata3 and Egr1, which are potent to regulate fibrosis-associated genes. Clinically, Regnase-1 protein levels in ILC2 negatively correlated with the ILC2 population in bronchoalveolar lavage (BAL) fluid. Furthermore, idiopathic pulmonary fibrosis (IPF) patients with more than 1500 cells·mL−1 peripheral blood ILC2s exhibited poorer prognosis than patients with lower numbers, implying the contribution of Regnase-1 in ILC2s for the progression of IPF.Collectively, Regnase-1 was identified as a critical posttranscriptional regulator of the pro-fibrotic function of ILC2s both in mouse and human, suggesting that Regnase-1 may be a novel therapeutic target for IPF.

Minimal Concentrations of Deoxynivalenol Reduce Cytokine Production in Individual Lymphocyte Populations in Pigs

Deoxynivalenol (DON) is a mycotoxin frequently found in cereals, and pigs are one of the most sensitive farm species to DON. The aim of this study was to determine the effects of DON in very low doses on peripheral blood mononuclear cells (PBMC) and on particular lymphocyte subpopulations. The cells were exposed to 1, 10 and 100 ng/mL of DON and lymphocyte viability, proliferation, and cytokine (Interleukin (IL)-1β, IL-2, IL-8, IL-17, Interferon (IFN) γ and tumor necrosis factor (TNF) α production were studied. Cells exposed to DON for 5 days in concentrations of 1 and 10 ng/mL showed higher viability compared to control cells. After 18 h of DON (100 ng/mL) exposure, a significantly lower proliferation after mitogen stimulation was observed. In contrast, an increase of spontaneous proliferation induced by DON (100 ng/mL) was detected. After DON exposure, the expression of cytokine genes decreased, with the exception of IL-1β and IL-8, which increased after 18 h exposure to 100 ng/mL of DON. Among lymphocyte subpopulations, helper T-cells and γδ T-cells exhibiting lower production of IL-17, IFNγ and TNFα were most affected by DON exposure (10 ng/mL). These findings show that subclinical doses of DON lead to changes in immune response.

Immunostimulating Activity of Gold-modified Nanodiamond Particles

Background: The fight against infectious diseases includes two main components – immediate direct anti-infective action and stimulation of one's own immunity. Objective: In this study, we investigated the properties of diamond nanoparticles modified with gold. The use of such gold nanoparticles as indirect anti-infectious agents and immunostimulators has certain prospects. Material and Methods: Gold hydrosols were synthesized by the reduction in an aqueous solution of gold (III) with sodium citrate (Na3Cit) under heating. Modification procedure of nanodiamond by gold requires incubation, a small sample of nanodiamond in a defined volume of a gold sol for about 24 hours in a dark place. We use human blood cells as test objects. The reaction of blastic transformation of lymphocytes was applied here as a test of biological actions of modified nanodiamond. Results: Modified nanodiamond do not have a toxic influence on blood cells. Modified nanodiamond possesses stimulation effects on spontaneous proliferation of lymphocytes and does not significantly affect phytohemagglutinin-induced proliferation. Nanodiamond slightly increases phagocytosis parameters of neutrophil leucocytes. Conclusion: Thus, results showed that the nanodiamond modified by gold possesses immunostimulating activity, increases the phagocytic activity of neutrophilic leukocytes and stimulates lymphocytes in the spontaneous proliferation test. Gold-modified nanodiamond could be considered as a non-direct anti-infective agent through immune stimulation.

Transcription factor KLF2 regulates homeostatic NK cell proliferation and survival

Natural killer (NK) cells are innate lymphocytes that recognize and lyse virally infected or transformed cells. This latter property is being pursued in clinics to treat leukemia with the hope that further breakthroughs in NK cell biology can extend treatments to other cancers. At issue is the ability to expand transferred NK cells and prolong their functionality within the context of a tumor. In terms of NK cell expansion and survival, we now report that Kruppel-like factor 2 (KLF2) is a key transcription factor that underpins both of these events. Excision of Klf2 using gene-targeted mouse models promotes spontaneous proliferation of immature NK cells in peripheral tissues, a phenotype that is replicated under ex vivo conditions. Moreover, KLF2 imprints a homeostatic migration pattern on mature NK cells that allows these cells to access IL-15–rich microenvironments. KLF2 accomplishes this feat within the mature NK cell lineage via regulation of a subset of homing receptors that respond to homeostatic ligands while leaving constitutively expressed receptors that recognize inflammatory cytokines unperturbed. Under steady-state conditions, KLF2-deficient NK cells alter their expression of homeostatic homing receptors and subsequently undergo apoptosis due to IL-15 starvation. This novel mechanism has implications regarding NK cell contraction following the termination of immune responses including the possibility that retention of an IL-15 transpresenting support system is key to extending NK cell activity in a tumor environment.