CELLULAR IMMUNITY PARAMETERS IN PATIENTS WITH REMITTING MULTIPLE SCLEROSIS

The aim of this work was to study some parameters of cellular immunity in patients with multiple sclerosis (MS). The study included 10 patients with relapsing-remitting MS aged 32 to 50 years. Diagnosis was clinically established and confirmed by magnetic resonance imaging. Patients did not receive immunosuppressive therapy for at least 6 months prior to study entry. The neurological status of all examined patients was assessed using the Kurtzke functional scale using the Extended Disability Scale (EDSS) and averaged 4.0±0.67 points, the mean number of exacerbations per year was 1.25±0.25. While studying such parameters of the immune status such as the number of T, B, NK-cells, the content of immunoglobulins, the phagocytic activity of monocytes and granulocytes, their production of reactive oxygen species, no significant differences were observed in patients with MS in comparison with the normal donor level. At the same time, we have noted an increase in the proliferative response of mononuclear blood cells to myelin antigen by 2.35 times. The content of CD4+CD45RO+CD62L+ and CD8+CD45RO+CD62L+ central memory T-cells, as well as CD8+CD45RO+CD62L- effector memory T-cells in the blood of MS patients significantly exceeded the control values (p < 0.05). Also, in MS patients, compared with healthy individuals, there was an increased level of naive IFNγ-positive CD4+CD45RO- and CD8+CD45ROT-cells (p < 0.01), and an increase in CD4+CD45RO+ and CD8+CD45RO+ memory T-cells producing IFNγg or IFNγg together with IL-4 in response to the activation (p < 0.01). Consistent with these data, there were significantly increased serum IFNγ and IL-17 levels and no changes in IL-4 levels. The relative level of naive CD4+CD25+FoxP3+, as well as induced CD4+CD25- FoxP3+ regulatory T-cells in MS patients did not significantly change compared to donor values. The results of assessing some parameters of the immune status in MS patients indicate a functional reshaping of the immune system towards the Th1 type of immune response. It is obvious that immunotropic treatment of MS should be aimed at inactivating auto-immune Tand B-lymphocytes, suppressing the production of proinflammatory mediators, and enhancing the activity of natural and induced regulatory T-cells

CONTENTS OF REGULATORY T-CELLS IN PERIPHERAL BLOOD AND ENDOMETRIAL TISSUE IN DYNAMIC OF MENSTRUAL CYCLE

The maintenance of CD4+CD25+/high and CD4+CD25+CD127 — regulatory T-cells in a peripheral, menstrual blood and an endometrial tissue in different phases of a menstrual cycle is investigated. It is shown that in a phase of average secretion the number of regulatory T-cells is increased. Thus quantity of CD4+CD25+increased in peripheral circulation, and in an endometrial tissue number of CD4+CD25+CD127- cells grew

Taxonomic composition and biodiversity of the gut microbiome from patients with irritable bowel syndrome, ulcerative colitis, and asthma

To date, the association of an imbalance of the intestinal microbiota with various human diseases, including both diseases of the gastrointestinal tract and disorders of the immune system, has been shown. However, despite the huge amount of accumulated data, many key questions still remain unanswered. Given limited data on the composition of the gut microbiota in patients with ulcerative colitis (UC) and irritable bowel syndrome (IBS) from different parts of Siberia, as well as the lack of data on the gut microbiota of patients with bronchial asthma (BA), the aim of the study was to assess the biodiversity of the gut microbiota of patients with IBS, UC and BA in comparison with those of healthy volunteers (HV). In this study, a comparative assessment of the biodiversity and taxonomic structure of gut microbiome was conducted based on the sequencing of 16S rRNA genes obtained from fecal samples of patients with IBS, UC, BA and volunteers. Sequences of the Firmicutes and Bacteroidetes types dominated in all samples studied. The third most common in all samples were sequences of the Proteobacteria type, which contains pathogenic and opportunistic bacteria. Sequences of the Actinobacteria type were, on average, the fourth most common. The results showed the presence of dysbiosis in the samples from patients compared to the sample from HVs. The ratio of Firmicutes/Bacteroidetes was lower in the IBS and UC samples than in HV and higher the BA samples. In the samples from patients with intestinal diseases (IBS and UC), an increase in the proportion of sequences of the Bacteroidetes type and a decrease in the proportion of sequences of the Clostridia class, as well as the Ruminococcaceae, but not Erysipelotrichaceae family, were found. The IBS, UC, and BA samples had signif icantly more Proteobacteria sequences, including Methylobacterium, Sphingomonas, Parasutterella, Halomonas, Vibrio, as well as Escherichia spp. and Shigella spp. In the gut microbiota of adults with BA, a decrease in the proportion of Roseburia, Lachnospira, Veillonella sequences was detected, but the share of Faecalibacterium and Lactobacillus sequences was the same as in healthy individuals. A signif icant increase in the proportion of Halomonas and Vibrio sequences in the gut microbiota in patients with BA has been described for the f irst time

EFFECTS OF MEVALONATE PATHWAY MODULATORS UPON REACTIVITY OF MACROPHAGES IN E XPERIMENTAL NEPHROSCLEROSIS

Abstract. The effects of cholesterol (Ch) diet, i.p. administration of mevalonic acid (Mev) and their combined application upon nitric oxide (NO) production in peritoneal macrophages, as well as upon biochemical characteristics of kidney function derangements, and histological parameters of tissue alterations, infiltration and fibrosis were studied in experimental model of chronic rhabdomyolysis-induced renal injury induced in C57Bl/6 mice. The effects of Ch diet, Mev and their combination on the degree of renal fibrosis were also studied in a model of unilateral ureteral obstruction. In normal animals, and, especially, in nephrotic mice, Ch diet was shown to cause a dramatic decrease of LPS-induced NO production, whereas Mev did enhance NO production significantly. Administration of Mev during Ch treatment abolished, in part, the suppressive effect of Ch. Ch diet was shown to enhance fibrotic response, without significant effect upon tissue alteration and mononuclear infiltration, whereas Mev enhanced alterative component and slightly diminished fibrosis. We conclude that Ch diet and Mev exert opposite effects upon the course and outcome of chronic nephropathy for their inhibitory (Ch) and stimulating (Mev) effect on mevalonate pathway, which is involved in the control of macrophage M1-M2 polarization

CLINICAL AND IMMUNOLOGICAL ASPECTS OF T C ELL-BASED VACCINE THERAPY IN PATIENTS WITH PROGREDIENT MULTIPLE SCLEROSIS

Abstract. Thirty-nine patients with a progredient clinical form of chronic multiple sclerosis (MS) were subject to multiple immunization with autologous polyclonal T-cell vaccines. Two years after initiating the vaccine therapy, no evidence for disease progression was noted in 16 patients (41% of total). Neurological improvement was observed in five cases (13%) from the vaccine-treated group. Of 22 control MS patients who did not receive the immunotherapy, only 6 persons (27%) exhibited stabilization of their clinical state. Clinical improvement was not detectable among this group of MS patients. A group of twenty-six MS patients was treated with Rebif, without evidence of disease progression in eleven cases (42%), and distinct neurological improvement noted in one patient (4%) from this group. One year after starting the vaccine therapy, a rise in serum IL-10 was detected in vaccine-treated patients, whereas IL-17 and IL-18 serum levels remained within the initial ranges. A correlation between the serum levels of anti-myelin antibodies and appropriate anti-idiotypic antibodies was revealed in these patients. In general, the results obtained suggest polyclonal T-cell vaccination as a potentially effective treatment approach, both at early and more advanced stages of the disorder

A ROLE FOR INTERLEUKIN 8 IN DIRECT REGULATION OF T CELL FUNCTIONAL ACTIVITY

CD3+T lymphocytes were isolated from normal donors by positive magnetic separation. Activation of the T cells with particles conjugated with antibodies to CD3, СD28 and СD2 molecules led to substantial increase in T cell production of interleukin-8 (IL-8). An interleukin-8 receptor (CXCR1, CD181) was initially expressed in 13.3% of T lymphocytes. Activation of T lymphocytes resulted into a detectable increase of CD181+ cell number among CD4+ naïve cells and CD4+ terminally-differentiated effector cells, and, conversely, into decrease of their number among CD4+ effector memory cells. Activation of T lymphocytes was assessed by membrane expression of CD25 molecule (receptor for IL-2). IL-8 (0.01-10.0 ng/ml) was shown to markedly reduce activation of both CD4- and CD4+ effector memory T cells, as well as terminallydifferentiated T effectors, without significantly affecting activation of naive T lymphocytes and central memory T cells. IL-8 noticeably increased IL-2 production by activated Т cells, caused a reduced IL-10 production, and did not significantly affect the secretion of IFNγ and IL-4. The data obtained suggest a significance of IL-8 for direct regulation of adaptive T cell responses

DENDRITIC CELLS AS POSSIBLE REGULATORS OF IMMUNE RE-ORGANIZATION IN PREGNANCY

Abstract. The present work was aimed to evaluation of phenotype and functional properties of IFNα-induced dendritic cells (DCs) in normal pregnancy, and in cases complicated with suprarenal hyperandrogenia (HA), as well as in vitro assessment of dehydroepiandrosterone sulfate (DHEAS) effects upon DC functions. As compared with non-pregnant women, DCs from healthy pregnant women are notable for impaired maturation/activation, whereas fractions of mature (CD83+) and activated (CD25+) cells DC were similar in normal pregnancy and in women with HA. Blood sera from healthy pregnant women inhibited generation of mature DCs, whereas sera of women with HA and direct supplementation with DHEAS enhanced maturation and activation of DCs. Functional analysis of DC capacity to stimulate Th1 (IFNγ) and Th2 (IL-4) cytokine expression in MLC has shown that, in contrast to non-pregnant women with T1-cell activation by DCs, the DCs from healthy pregnant women caused predominant activation of CD3+IL-4+Т-cells. In HA-complicated pregnancy, DCs were capable to stimulate both Th1- and Th2-cytokine production in T-cell populations. Meanwhile, addition of DHEAS to DCs cultures were accompanied by enhancement of their T1- polarizing activity. DCs from women with normal pregnancy exerted inhibitory effect upon activated NK-cells that was evidenced by a relative decrease in CD56+CD16+ cells counts and increased apoptosis levels. This function of DCs was partially abrogated in presence of DHEAS. The results obtained reveal new mechanisms of immune/ endocrine nteractions in normal and complicated pregnancy

EVALUATION OF CELLULAR IMMUNE RESPONSE DURING XENOVACCINE THERAPY OF THE PATIENTS WITH STAGE IV OF COLORECTAL CANCER

Abstract. Thirty-seven patients with stage colorectal cancer stage IV were subjected to immunotherapy using a polyantigenic vaccine, prepared, basically, from lyzed cells of murine melanoma (B16) and murine carcinoma (LLC) cells. The inducing course of xenovaccine therapy consisted of 10 subcutaneous immunizations (5 injections weekly followed by 5 bi-weekly). Consolidating treatment included monthly vaccinations. Ther xenovaccine therapy was not associated with any serious adverse effects, and did not influence the composition of blood lymphocyte subsets. Significant increase in cellular immune reactions to vaccinal carcinoma-associated antigens occurred in the patients after an inducing treatment, as determined by both skin and antigen-driven blastogenesis test. The overall 2-year survival of thirty-seven stage IV colorectal cancer patients was shown to be significantly better, than in control group (37 clinically comparable patients), with median survival rates of 17 and 7 months, respectively

Production of IL-10, TNF-alpha, IFN-gamma, TGF-beta1 by different populations of erythroid cells derived from human embryonal liver.

It has previously been determined that erythroid cells of mice are capable of expressing such cytokines as interleukin (IL) 1 alpha and beta, IL-4, IL-6, interferon gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta (TGF-beta). It has been shown that glycophorin A(+) (GlA(+)) and antigen erythroblasts (AG-EB(+)) (both human erythroid cells of embryonic origin) are also capable of producing a series of cytokines such as IL-1 beta, IL-2, IL-4 and IL-6. The aim of this work was to study the capacity of erythroid cells from human embryonic liver to produce such cytokines as IFN-gamma, TGF-beta1, tumour necrosis factor alpha (TNF-alpha) and IL-10. The erythroid cells were isolated by means of antibodies specific to erythroblasts (GlA and AG-EB), as well as those from single erythroid colonies. The production level of some cytokines varies insignificantly under the action of erythropoietin (Epo) and quantitatively differs in GlA(+) and AG-EB(+) erythroid cells. Hence, the erythroid cells express IFN-gamma, TGF-beta1, TNF-alpha and IL-10. The erythroid cells could be involved through the production of these cytokines in the regulation of such processes as self-renewal, proliferation and differentiation of cells of other blood-forming sites