[Gene-engineering technologies and stem cells].

In the review it has been presented the conceptional analysis of modern state of stem cells use problem (SC) in gene therapy ex vivo. Principles of vectorial systems construction have been expounded, designed for SC transfection. It has been displayed results of experimental investigations and clinical data on transplantation of genetically modifiable SC at different monogenous and multifactorial diseases. Special attention is focused on the problem of biosecurity ensuring.

[The role of Toll-like receptors in regulation of immune responses in norm and pathology].

We have analyzed the recent data about Toll-like receptors (TLRs) that play the most important role in host immune defense. TLRs involved in induction and modulation of innate and acquired immunity as the integrators of their reactions. Genetic disorders of TLRs or their signaling pathways components were noticed with different pathologies. TLRs are the ideal molecular target for the therapy of many diseases including inflammatory, autoimmune, allergic and tumor diseases.

[Heat shock proteins and their role in the development of pathological processes].

Heat shock proteins (HSPs) are the most conserved proteins present in the archea, pro- and eukaryotes. HSPs have a dual function depending on their intra- or extracellular location. Intracellular HSPs play a cytoprotective role providing the cells with mechanisms to prevent damage caused by misfolded, damaged, aggregated, or insoluble proteins. Extracellularly located or membrane-bond HSPs participate in both innate and adaptive immune responses. The recent review focuses on the role of HSPs in the pathogenesis of infections, autoimmune, cardiovascular, oncological, neurodegenerative, and other diseases. HSPs may serve as potential molecular targets for therapeutic intervention in the treatment of various diseases, including cancer, Alzheimer's and Parkinson's diseases. Some HSPs may be used as immunoadjuvants or as HSP-based vaccines for the treatment of infections and cancers.

[Role of heat shock proteins in developing of innate immunity reactions].

Increasing interest to heat shock proteins (HSP) from biologists and medics is connected to widespread distribution of HSP in live nature and reflects their key role in support of life functions which is based on the unique polyfunctionality of these biomolecules. Together with main function, which is defense of biologic systems from stress effects, some HSP in the process of evolution acquired the ability to incorporate in the reactions of the immune system. The in vestmen of this protein in practical reactions of innate immunity system are described. Analysis of mechanisms underlying the adjuvant effect of pro- and eukaryotic HSP in innate immunity system is presented. HSP receptor structures on target cells as well as triggered intracellular signaling pathways are described.

[Mesenchymal progenitor cells. Biological characteristic and prospects for their use].

Imunophenotic characteristic of the mesenchymal stem and progenitor cells, their tissue origin and functional peculiarities as well as immunological aspects of its transplantation are presented in the article. Also the address migration and the site-specific differentiation of mesenchymal stem cells its age-related and pathological process induced changes are discussed. Prospects of clinical use of mesenchymal stem cells for the treatment of degenerative arthritis, spinal cord injuries, myocardial infarction and other disorders are shown.

[Current views on the biology of the stem cell]. / Sovremennye predstavleniia o biologii stvolovoi kletki.

Stem cells (SC) represent a unique cell population capable of self renewing and differentiation. Embryonal SC, represented in the internal cell mass blastocyst, give rise to cells of all three germ leaves. SC are also represented in many tissues of the adult organism. Their physiological function consists in renewing or restoration of the differentiated cells pool during the life span of the organism. The majority of regional SC of the adults differentiate into the limited number of cell types though some regional SC have a wider differential potential. Perfection of SC investigation methods at the molecular genetic level will help to reveal subtle mechanisms of these cells functioning.

[Production of interleukin-1 and interleukin-6 in a culture of mononuclear cells of peripheral blood and bone marrow in multiple myeloma]. / Produktsiia interleikina-1 i interleikina-6 v kul'ture mononuklearnykh kletok perifericheskoi krovi i kostnogo mozga pri mielomnoi bolezni.

Constitutive and lipopolysaccharide (LPS)--induced production of interleukin (IL)-1 and IL-6 have been investigated in peripheral blood (PB) and bone marrow (BM) of patients with multiple myeloma (MM) and PB of health donors. The level of these cytokines has been higher in MM in comparison with norm. Monocytes of PB of patients with MM have been more stimulated by LPS than those of health people. When adherent and nonadherent cells have been cultured apart, there not have not been any differences in constitutive IL-6 production between compared groups. The important role of cell-cell interactions in regulation of IL-6 production is proposed. High level of IL-6 in BM of patients with MM is conditioned by mutual stimulation of adherent and nonadherent cells.

[Role of humoral factors in the regulation of hemopoiesis in stress]. / Rol' gumoral'nykh faktorov v reguliatsii gemopoeza pri stresse.

The change of 11-1, IL-3, CSA concentrations in adherent and nonadherent bone marrow cells condition medium at stress were investigated. The activation of bone marrow hemopoiesis was registered at mice after immobilization stress. The number of CFU-GM increased on 1, 4 and 5 day after stress. Maximum of CSA in adherent and nonadherent cells conditioned medium was observed on day 4, 6 or 2, 5 respectively. The increasing of 11-3 activity in culture of nonadherent bone marrow cells was registered from day 1 and mount to maximum at 4-5 days. The increasing of 11-1 level in culture of adherent bone marrow cells was found at 1 and 4 days.

[The lack of generalized immunosuppression in C57BL/6 mice during progressive growth of syngenic T lymphoma EL-4 and Lewis lung carcinoma 3LL]. / Otsutstvie generalizovannoi immunosupressii u myshei linii C57Bl/6 pri progressiruiushchem roste singennykh T-limfomy EL-4 i legochnoi kartsinomy L'iuisa 3LL.

The immune competence of C57Bl/6 mice implanted with EL-4 lymphoma of Lewis Lung carcinoma 3LL was investigated during 3 weeks after implantation. Splenic lymphocyte responses to mitogens (Con A, PHA, LPS, PWM) cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2) production were assessed. A dramatic reduction in mitogenic responses to Con A and PHA was observed during tumour progression. LPS and PWM responses were less depressed. Con A-induced IL-2 production correlated with Con A and PHA responses. Allospecific CTL response to mastocytoma P 815 was not decreased in syngeneic tumour-bearing mice.

[Interleukin-2 restoration of the activity of natural killers during stress]. / Vosstanovlenie interleikinom 2 aktivnosti estestvennykh killerov pri stresse.

Interleukin 2 used in vitro and in vivo induces effectively the recovery of cytotoxic activity of natural killers and lectin-dependent cellular cytotoxicity effectors in stress-immobilized CBA mice. This lymphokin can be used for correction of stressor depression in the cells of the natural anti-tumor resistance system.

[The natural killer system in the human fetus]. / Sostoianie sistemy estestvennykh killerov u ploda cheloveka.

Natural cytotoxic activity of cells from human fetal spleen, liver, bone marrow, appendix, tonsilar glands and thymus was investigated in 14-26-week-old embryos. The spleen and liver expressed powerful NK activity against K-562 target cells from a 22 week-old embryo. Thymocytes and cells from the appendix and tonsilar glands displayed but negligible cytotoxic activity.

[Lectin-inducible cell cytotoxicity and the production of the cytotoxic factor of natural killer cells during immobilization stress in mice]. / Indutsiruemaia lektinom kletochnaia tsitotoksichnost' i produktsiia tsitotoksicheskogo faktora normal'nykh killernykh kletok pri immobilizatsionnom stresse u myshei.

Mice exposed to immobilization stress manifested a dramatic lowering of the activity of normal killers against YAC-1 tumor as well as against the lectin-induced cellular cytotoxicity mediated by Helix pomatia agglutinin and detected by the cytolytic test against xenogeneic tumor cells K 562. Exposure to stress did not provoke any change in the production of cytotoxic factor of normal killers, whereas dexamethasone (5 X 10(-7) M) in vitro inhibited the production of this factor.

Bone marrow suppressor B cells in vitro.

Marrow cells from intact CBA and (CBA x C57B1)F1 mice added to a culture of syngeneic splenocytes at its initiation suppressed the generation of anti-SRBC antibody-forming cells. Removal of cells bearing surface immunoglobulins and/or MBLA led to a substantial reduction in the marrow suppressive activity. Marrow cells from mice pretreated with five doses of hydroxyurea did not suppress the immune response of syngeneic splenocytes to SRBC. While the total number of cells in the marrow of such animals declined 5-fold, the relative content of Ig-positive cells was somewhat increased. The proportion of blast cells dropped from 10.3 to 2.4%. No blast cells bearing surface immunoglobulins were observed. The proportion of cells incorporating [3H]-thymidine fell 40-fold. We conclude that suppression of the immune response to SRBC in vitro is mediated by immature precursors of the B lymphocyte series which are present in the bone marrow of intact mice.

[Immunoglobulin-positive cells in mouse bone marrow]. / Issledovanie immunoglobulin-pozitivnykh kletok v kostnom mozge myshi.

The content of Ig-bearing lymphocytes and their precursors in the mouse bone marrow was investigated 6 and 36 hours after the hydroxyurea treatment. Some increase of the B-cell content takes place in the trated bone marrow. Dividing and non-dividing B-cell precursors, except the stem cells, were practically absent.

[Electrophoretic and immunologic characteristics of the Fc+ and Fc- fractions of the splenic cells of CBA mice]. / Elektroforeticheskaia i immunologicheskaia kharakteristika Fc+ i Fc--fraktsii kletok selezenki myshei CBA.

Conditions have been established for the effective separation of Fc+ and Fc- cells, using sheep red blood cells monolayer, sensitized with the anti-SRBC antibodies. The method was modified by replacement of poly-L-lysine by protamine sulfate. The electrophoretic distribution profiles of Fc+ and Fc- mouse splenocytes were determined. Fc+ cells had mostly a slow electrophoretic mobility. The Fc- cells were more mobile. The Fc+ fraction contained mainly B-lymphocytes, and the Fc- fraction was enriched with T cells. There was an extensive overlap between the electrophoretic profiles of the Fc+ and Fc- splenocytes. After the splenocyte passage through the glass bead column the overlap became much less.

[Antigen-binding clone cells in hematopoietic spleen colonies]. / Issledovanie klonov antigensviazyvaiushchikh kletok v krovetvornykh seleznochnkh koloniiakh

The antigen-binding cell clones and the Ig-positive cells were found and quantitatively assessed in the primary hemopoietic splenic colonies. The data ogtained were analyzed assuming that the ratio of clone of specialized B-cells should reflect the quantitative ration in the corresponding V-genes in the given lymphocyte populations at definite stages of its development. The colonies differed from one another markedly by the curves of inhibition by DNP-lysine of rosette-formation with DNP-erythrocytes, i.e. by the avidity of B-cells of the given specificity. The colonies differed significantly by the ratio of the volumes of the two clone groups (cell with anti-DNP and anti-BE Ig-receptors) between themselves and the combination of the Ig-positive cells. These quantitaive regularities were incompatible with the view that each B-cell had any conceivable set of V-genes, i.e. with the germ-line hypothesis of the antibody and receptor diversity.

[Role of macrophages in the mechanism of specific entrapment of sensitized lymphocytes in lymph nodes containing antigen]. / Issledovanie roli makrofagov v mekhanizme spetsificheskoi zaderzhki sensibilizirovannykh limfotsitov v limfaticheskikh uzlakh, soderzhashchikh antigen

A study was made of the participation of macrophages in the phenomenon of specific trapping of lymphocytes activated with the antigen in the lymph nodes containing the same antigen. Administration of peritoneal macrophages which phagocytized in vitro sheep erythrocytes (as well as of erythrocytes alone) led to specific trapping of lymphocytes in the regional lymph nodes. Preliminary treatment of macrophages loaded with the antigen with antierythrocytic serum decreased the lymphocyte trapping. A supposition was put forward that lymphocytes with receptors on their surface were bound on the macrophage membrane into which the antigen molecules were incorporated.