Analysis of regulatory T lymphocytes in fungal infections

Morbidity and mortality rates in invasive mycoses determine the need to improve methods for their timely diagnosis by assessment the patients’ immune status. Evaluation of individual immune status allows the clinician to predict the development and course of fungal infections. At the same time, identification of opportunistic mycosis in immunocompetent patients should require a search for some hidden immune deficiency. Determining the cause of such immune defects can help develop an effective strategy for both etiotropic and immune therapy of patients with invasive mycoses. Currently, the functions of regulatory T lymphocytes that support immunological tolerance in fungal infections remain to be incompletely studied. In this review, we present experimental works which suggest that the regulatory T lymphocytes are able to suppress immune responses to fungi by stimulating the immunosuppressive environment. It was shown that regulatory T lymphocytes use Toll-like receptor 2 to achieve immunosuppression in Candida infections. The balance between the number and function of regulatory T lymphocytes is essential for elimination of fungal pathogens and protection against post-infectious immunopathological conditions. It was found that the regulatory T lymphocytes provide protection at an early stage of Candida infection, since, due to IL-2 suppression, they enhance Th17 differentiation and clearance of fungi. Moreover, at the later stages of infection, the regulatory T lymphocytes have an inhibitory effect. The balance between Th17 and regulatory T lymphocytes in mucosal lining is considered the main factor for distinguishing between commensal carriage and Candida albicans infection. The study is presented which indicate that disseminated candidiasis associated with expansion of regulatory T lymphocytes stimulates a Th17-cell response that controls the course of the disease. The mechanisms that control regulatory T lymphocytes homeostasis are essential for providing effective protection against pathogens, as well as for controlling the immunopathological conditions associated with Candida infection. The review presents data that have established the role of TGF-β1 in increasing the viability of regulatory T lymphocytes, which is correlated with the pronounced immunomodulating role of these cells at the later phase of Candida infections of the mucous membrane. It has been also demonstrated that the pulmonary regulatory Tlymphocytes are induced during cryptococcal infection, which predominantly suppresses Th2 cells, thereby supporting its course. Expansion of the regulatory T lymphocytes upon administration of IL-2/antiIL-2 complex during cryptococcal infection led to a decrease in IgE production and a decrease in allergic airway inflammation. It should be noted that refinement of prognostic value of the regulatory T lymphocytes in human fungal infections may substantiate the basic principles of targeted immunotherapy

ROLE OF THE REGULATORY T CELLS IN PROGRESSION OF PROSTATE CANCER

The existing data on regulatory T cells (Tregs) in prostate cancer suggest that these cells may penetrate the prostate gland malignant tissue, suppressing antitumor immune response, thus promoting aggressive clinical course and low survival of the cancer patients. Evaluation of T cell subpopulations from the tumor microenvironment has shown that the number of CD4+Tregs is associated with inferior clinical prognosis. In particular, each additional CD4+Treg cell has been shown to cause a statistically significant increase in prostate cancer mortality by 12%, regardless of other clinical factors. There are several possible explanations for the increased infiltration of prostate cancer tissue with regulatory T cells. Firstly, malignant cells or tumor-associated macrophages are capable of secreting chemokine CCL22, which has an affinity for the CCR4 receptor expressed on Treg cells. Secondly, cytokines secreted by prostate tumors, such as TGF-β, may regulate the FoxP3 expression, thus expanding the Treg population. TGF-β, in turn, is a multifunctional cytokine that promotes survival and proliferation of transformed cells, including prostate epithelium, as evidenced by increased amounts in the patients with metastatic disease

CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY

Despite numerous attempts to control the course of chronic rhinosinusitis with nasal polyps (CRSwNP) by means of pharmacological treatment and new surgical approaches, the majority of patients experience lifelong persistence of this disorder, at recurrence rates of 50-60% within 18 months after surgical treatment. Since CRSwNP is a chronic persistent inflammatory process, it affects the entire body condition, including the state of systemic immune response. An elevation of NK (CD3-CD16+CD56+), activated NK (CD8+CD3-), NKT cells (CD16+CD56+CD3+), Treg (CD4+CD25brightCD127low to neg) cells and activated T-lymphocytes (CD3+CD25+) was revealed elsewhere among all the patients with CRSwNP, using a flow ytometry method. There was no difference between various disease phenotypes. We analyzed the status of cellular component of systemic immunity, dependent on clinical course of the disease and efficiency of the administered therapy of CRSwNP. The patients were divided into three subgroups. The follow-up period was 1 year. The first group comprised the patients who showed positive dynamics after conservative therapy, resulting into regression of nasal polyps and their grade than a year ago. The second group included the patients in whom the size of polyps remained the same. The third group included the patients with higher incidence of nasal polyps than a year ago.We have shown a decrease of Treg, NKT cells, NK and activated NK, cytotoxic T-lymphocytes (CD3+CD8+), activated T-cell numbers in clinical group 3 with aggressive growth of polyps and low effect of standard therapy, which may cause deterioration of the immune system cellular populations, accompanied by presence of persistent productive inflammatory process of nasal cavity and paranasal sinuses. In the second group, a significant elevation of total lymphocyte number, total and activated T cells, T helpers (CD3+CD4+), cytotoxic T lymphocytes, NK and NKT cells was shown. Meanwhile, a decrease in absolute number of activated NK was observed despite the NK growth. Therefore, we can assume that the mechanism of their activation was disturbed and compensated by production of NKT cells and cytotoxic T lymphocytes. Moreover, we have shown in this group that the absolute number of Treg cells is increased; and these cells had a suppressive influence on effector cells of adaptive immune response, thus inducing incomplete elimination of infectious agents, which contribute to permanent incomplete course of inflammatory process. Chronic inflammatory process in CRSwNP affects systemic cellular immunity depending on the morbidity characteristics in the course of pathological process. The maximal intensity of systemic cellular immunity is observed in the group of patients that require permanent basic drug therapy. In case of aggressive CRSwNP and failure of standard drug therapy, we observed a decrease in absolute numbers of effector cells, along with decreased Treg lymphocyte numbers which may explain inefficient immune regulation of inflammatory process and medical interventions in this group of patients

Luminescence of Ce3+ multicenters in Ca2+ -Mg2+ -Si4+ based garnet phosphors

Comparison of the luminescent properties of Ca3Sc2Si3O12: Ce and Ca2YMgScSi3O12: Ce single crystalline films (SCF) phosphors, grown by the liquid phase epitaxy method, was performed in this work. We have observed formation of the Ce3+ multicenters in Ca3Sc2Si3O12: Ce and Ca2YMgScSi3O12: Ce in the emission and excitation spectra as well as in the decay kinetics of the Ce3+ luminescence in SCFs of these garnets. Such Ce3+ multicenters possess different crystal field strength due to the inhomogeneous local surroundings of the dodecahedral positions of garnet host at the substitution of the octahedral positions by hetero-valence Mg2+ and Sc3+ ions and the tetrahedral positions by Si4+ ions. We confirm the presence of an effective energy transfer between different Ce3+ multicenters in Ce3+ doped Ca3Sc2Si3O12 and Ca2YMgScSi3O12 garnets. The positive trends in variations of the spectroscopic properties of the Ca2YMgScSi3O12: Ce garnet with respect to Ca3Sc2Si3O12: Ce garnet were observed also due to substitution of the dodecahedral sites of the garnet host by Y3+ ions and the octahedral sites by Mg2+ ions, which can be suitable for the development of new converters of white LEDs. Namely, due to the Y3+-Mg2+ doping, the luminescence spectrum of Ce3+ ions in Ca2YMgScSi3O12: Ce SCFs significantly extends in the red range in comparison with the Ca3Sc2Si3O12: Ce SCF counterpart

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

MINOR SUBSETS OF T-HELPER CELLS (Th THYMIC NAIVE, Th CENTRAL NAIVE, Th9, Th22 AND CD4+CD8+ DOUBLE POSITIVE T-CELLS)

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

APPROACHES TO STANDARDIZATION OF THE FLOW CYTOMETRY METHOD FOR CELLS IMMUNOPHENOTIPING. CYTOMETRS ADJUSTMENT AND PREPARATION OF PROTOCOLS FOR ANALYSIS

Abstract. Immunophenotyping by using a flow cytometry method allows characterizing cells with the help monoclonal antibodies or any other probes and enables to judge their type and a functional condition on presence of this or that set of cellular markers and processes occurring in them. However as a result of carrying out cytometryc analysis could be a number of mistakes at different stages of preparation cytometer to work and that leads to not correct result. To avoid it, the algorithm of preparation of reports for the analysis of cells of peripheral blood is offered. This algorithm of adjustment of the working report looks as follows: check of cytometers work; adjustment of the discriminator; adjustment of sensitivity of channels of light scatters; sensitivity adjustment of channels of fluorescence; introduction of factors of indemnification. Standard adjustments flow cytometers and reports will allow carrying out more correctly the analysis as in clinical diagnostic, and the research purposes

OPPORTUNITIES OF FLOW CYTOMETRY IN DIAGNOSTICS OF INFECTIOUS DISEASES. Part 2

Abstract. Flow cytometry allows estimating quantitative and qualitative structure of populations and subpopulations of immune system cells by using various methodical approaches and a wide spectrum of reagents. For diagnostics the Acquired Immune Deficiency Syndrome (AIDS) caused by a Human Immunodeficiency Virus (HIV) the flow cytometry became irreplaceable. Traditionally, immunologists examine standard model of an estimation of immune dysfunction on the basis of classical markers of Т-cells (CD3, CD4, CD8) at the HIV-infection. But researchers pay less attention to other populations and subpopulations of lymphocytes, such as γδ-, αβ- and CD38+ Т-cells. The quantitative estimation of these parameters from a HIV and AIDS patients enables to see pathogenesis a HIV infection and the prediction of its development from another side