Abstract. T cell populations, specifically, T helper (Th) cells, are among key players in the processes occurring in the body following exposure to a foreign antigen. Usage of new, highly sensitive instruments allowed of more detailed studies of their structural arrangement, as well as to detect a number of functionally significant minor subsets. These T cell subtypes were characterized both phenotypically and functionally. Present review article concerns Th thymic naїve subsets, Th central naїve subpoppulations, Th9, Th22, and CD4+CD8+ doublepositive T cells. Their role and functional significance is discussed in various pathological conditions. At present time, there are convincing data about specific arrays of membrane molecules, transcription factors, production of specific mediators typical to either of these subsets. Application of these markers in laboratory studies, will certainly improve diagnostic quality when evaluating functional alterations of immune system and adequacy of prescribed immunotherapy.

Abstract. This paper presents the results of the research on the effectiveness of recombinant TNF-binding protein of variola virus (VARV-CrmB) in a model of collagen-induced arthritis (CIA) in mice (CBAxC57Bl6) F1. The introduction of VARV-CrmB and polyclonal antibody to recombinant mouse TNF (poly-AbMuTNF) led to an improvement of clinical manifestations of CIA by reducing the swelling and increasing the mobility of mice limbs. The introduction of VARV-CrmB and poly-AbMuTNF reduced the number of neutrophilic granulocytes and granulocytic precursors. The introduction of VARV-CrmB and poly-AbMuTNF into mice decreased collagenolysis in the blood serum and the content of glycosaminoglycans at the early stages of experimentation. Treatment with VARV-CrmB and poly-AbMuTNF of mice with CIA significantly decreased the chemiluminescence response of blood leukocytes. VARV-CrmB exerted more pronounced inhibitory effect on the production of reactive oxygen metabolites by blood leukocytes of mice with CIA than poly-AbMuTNF. Improvement of clinical condition of the mice with CIA has a more prolonged effect following introduction of the VARV-CrmB than after injection of poly-AbMuTNF. The results suggest the recombinant viral protein VARVCrmB to be a new potential TNF-antagonist.

Abstract. Chemokines are generally believed to play an important role in immunopathogenesis of different joint diseases. Synovial fluid is the primary bio-material, along with peripheral blood, for evaluation of patients with joint pathology (rheumatoid arthritis, osteoarthritis, psoriatic arthritis, etc). However, analysis of synovial membranes is also of importance, since the main pathologic processes evolve at this site. Analysis of chemokines and their receptors in synovium may provide more complete information about immunopathogenesis of articular disease of different etiologies. We carried out optimization procedures for real-time reverse-transcription PCR analysis, in order to quantify specific mRNA expression of angiogenic and angiostatic chemokines and their receptors in synovium. All the stages, from sampling the biological material and until analysis of results are described in details. Normal ranges for mRNA expression rates are provided, as based on examination of subjects with previous traumatic joint injury, without any clinical signs of current systemic or local inflammation. We demonstrate that this method can be informative for comparing intra-articular expression of chemokines and their receptors between different clinical groups. It can also be used to investigate the role of chemokines in appropriate immunopathological events.

Abstract. Objectives: Chronic viral hepatitis В (CHB) and С (CHC) comprise an important issue of modern pediatrics. Immunogenetic disorders are among key factors of their pathogenesis. The aim of present research was to reveal interactions between polymorphisms of cytokine IL-1β and IL-6 genes and clinical characteristics of the disease in children.

The study included forty-eight children aged from 6 to 17 years (a median of 12 years old), including thirty patients with CHC, and eighteen – with CHB. Polymorphism of cytokine genes – interleukin 1β (IL-1β) – T31C, interleukin 6 (IL-6) – G174C was evaluated by means of allele-specific polymerase chain reaction (PCR); the amplification products were detected by horizontal electrophoresis (“Litekh”, Russia).

The groups of CHB and CHC patients were characterized by increased prevalence of CC genotype of IL- 1β Т/С -31gene and СС genotype of IL-6 -174 G/C gene variants, as compared to control group [OR = 3.66 (95% CI – 1.2-11.0) and OR = 2.81 (95% CI – 1.33-5.87)]. The IL-6 -174 G/C polymorphism of is associated with higher IL-1β synthesis in GG genotype carriers, when compared to GC (p = 0.016) and СС genotypes (p = 0.030). In children with active CHB and CHC, polymorphisms of IL-1β -31 ТС and СС, as well as IL-6 -174 СC, were related to the higher cytolysis level, while the genotypes IL-1β -31 ТТ and IL-6 -174 GC and GG – with absence of cytolytic features(p = 0.022; p = 0.038).

Presence of polymorphisms of IL-1β and IL-6 genes may sufficiently contribute to susceptibility to chronic hepatitis development and have an impact on extent of clinical and immunological presentations of the disease.

Abstract. The role of hepatitis C virus (HCV) co-infection in violation of restoring CD4+T cells in HIVinfected patients receiving antiretroviral therapy (ART) was investigated. Seventy eight patients with effective virological response to ART (viral load < 50 copies/ml) who either had or had no good immunological CD4+Tcell response after two years of treatment were recruited. Twenty one relatively healthy volunteers served as controls. The numbers of main T-lymphocyte populations and their apoptosis rates were determined. Thymus productive function was assessed by the number of αTREC-positive CD4+ and CD8+T cells. It is shown that HIV/HCV co-infection is characterized by lower numbers of CD4+T-lymphocytes in patients’ blood compared with HIV-monoinfection. This is not associated with the cells’ increased death rates. We also demonstrate that HCV coinfection reduces the production of CD4+, but not CD8+T-lymphocytes, by the thymus.

Abstract. We have studied possible interrelationships between immune system state and efficiency of neoadjuvant chemoradiotherapy in patients with cancer of larynx and hypopharynx. The neoadjuvant treatment consisted of 2 courses of paclitaxel (175 mg/m2), carboplatin (AUC-6 in 3-4 weeks), followed by radiation therapy at a multifraction dose schedule (1.2 Gy 2 times daily in 4 h, total cumulated dose was estimated as isoeffective dose of 40 Gy). A better response to chemotherapy by paclitaxel and carboplatin in the patients with cancer of larynx and hypopharynx had been associated with higher percentage of CD56+ cells and IgM levels in peripheral blood, as measured before starting cancer treatment. After completing the neoadjuvant chemo- and radiotherapy, we noted an increase in total lymphocyte counts, CD4+, CD8+, CD56+ cell numbers and IgG levels in the patients with pronounced response to chemotherapy, thus suggesting some induction of immune response in cancer patients during cytostatic therapy. These data presume a relationship between the state of immune system in the patients with head-and-neck cancer, and their response to neoadjuvant chemo- and radiotherapy. On the basis of these findings, one may suggest that immunological mechanisms make take an important part in promotion of antitumor effects produced by standard cancer treatment.

Abstract. Increased VEGF levels in cancer patients may be associated with decreased number of dendritic cells (DCs) and lower DC function. We investigated whether VEGF gene polymorphisms -2578C>A (rs699947) and +936C>T (rs3025039) are associated with efficacy of autologous DC-based immunotherapy in patients with malignant melanoma. Evaluation of VEGFR-1 and VEGFR-2 expression on mature monocyte-derived DC revealed a decreased VEGFR-1 level (18.9±0.7% on peripheral blood monocytes, as compared to 6.3±0.6% on mature DCs) and non-changed VEGFR-2 expression (13.1±0.4% and 15.9±0.4%, respectively). The АА genotype frequency of -2578C>A (rs699947) polymorphism of VEGF gene was 46.1%. АС heterozygous state was found in 38.5%, and СС, in 15.4% of cases. The VEGF -2578 AC and AA genotypes were directly associated with progression-free survival and efficacy of treatment. The median progression-free survival of patients with -2578 AA and AC genotypes was a significantly longer (8.4 months), as compared with that of patients with CC genotypes (2.7 months), p = 0.002. The established relationship between genotype and efficacy of immunotherapy can be used to develop modern methods for predicting melanoma progression and to personalize immunotherapy including a combination with antiangiogenic therapy.

Abstract. Cytokines play an important role in resistance to herpesvirus infections. Therefore, studies of cytokine profile are necessary in recurrent herpetic infection. However, functional studies of cytokine network upon remission of the disease yielded controversial results. In this paper, we provide some results concerning comprehensive evaluation of ex vivo cytokine production by whole blood leukocytes drawn from 15 patients observed during clinical remission of recurrent Herpes Simplex virus infection. We have found a decrease of IL-1β, IL-8 and IL-10 production, as well as imbalance of cytokine profile, with predominance of IFNγ and IL-8 synthesis over IL-10 production, along with increased IL-4 and IL-13 levels to IL-1β contents. Differently directed correlations between the content of activated lymphocytes (CD3+HLA-DR+ and CD3+CD4+CD25+), natural killers (СD3-СD16/56+), NKT-cells and cytokine production levels were found in the groups of patients and healthy individuals. These differences may be due to shifts in major cytokineproducing populations in herpesvirus infections.

Abstract. In this study, we have identified functional features of immune system cells in patients with acute lymphoblastic leukemia (ALL), depending on clinical stage of the disease. At all stages of the disease, the patients developed T-cell immunodeficiency. A decrease in T lymphocyte scores and diminished CD4/CD8 ratio was associated with development of primary ALL attack. An increase in NK-cells was typical to ALL relapse. In general, ALL cell populations were characterized by a significant reduction of intracellular metabolic processes in lymphocytes. Chemiluminescent activity of neutrophil granulocytes changed in ALL patients with disease progression, being intensified at the stage of primary attack, followed be decreased activity during complete clinical remission and relapse, probably, due to depletion of internal reserves. The study confirmed that significant changes in ALL are associated with functional and metabolic state of lymphocytes and neutrophils upon progression of the disease, which is probably responsible both for development of complications, but it also may influence relapse risks and determine worse prognosis in general.

Abstract. The role of immune factors in development of atherosclerotic process and anxiety-depressive disorders is of utmost importance. Serum levels of IL-6 and -10 were studied in forty-nine patients with acute coronary syndrome, as well as their interactions with psychological state of the patients. Serum concentrations of the cytokines proved to be higher in unstable angina. A correlation was confirmed between the cytokine levels and co-morbidity with affective disorders in acute ischaemic heart disease.