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Biomedical subjects

A A Iarilin

Publications and source records attributed to A A Iarilin.

At least 19 recordsLinked to original sources

[Consequences of interactions between thymic lymphoid and epithelial cells in vitro].

A 24-hour co-cultivation of thymocytes and epithelial cells taken from human thymus results in mutual activation of epitheliocytes and thymocytes, as well as in apoptosis of thymocytes. The apoptosis can also be induced by a cultural supernatant of the thymic-epithelial cells, its level being lower, however, than in the co-culture. Thymocyte death and elimination develop faster in a co-culture with allogeneic thymic epithelial cells.

Antigens, CD↗

[In vivo and vitro effects of interferon-alpha 2b on functional activity of T-lymphocytes from patients with rheumatoid arthritis].

AIM: To investigate the effect of recombinant alpha 2b-interferon (r alpha 2b-IFN) on functional capacity of peripheral blood (PB) T cells in rheumatoid arthritis (RA) patients and the relationship between functional characteristics of T lymphocytes and the disease activity. MATERIALS AND METHODS: PB mononuclear cells (PBMC) were separated by Ficoll-Verografine++ gradient centrifugation from 24 healthy donors (HD) and 75 RA patients 19 of which were treated with r alpha 2b-IFN (realdiron, Biofa, Lithuania) in the dosage 1 million IU i.m. each other day for 20 days, 10 injections a course. Cell surface markers (CD3, CD4, CD8) and adhesion molecules (CD18, CD54, CD2) were analyzed using specific monoclonal antibodies (MoAbs) and flow cytometry on the PBMC, freshly isolated and treated for 72 hours with medium alone, PHA, r alpha 2b-IFN and their combination. The proliferative response of PBMC to MoAbs for CD3, PHA and r alpha 2b-IFN were assessed by 3H-thymidine incorporation. The percentage of spontaneous and inducing apoptosis was quantified by flow cytometry using propidium iodide staining. RESULTS: The expression of CD18 was lower on RA PB lymphocytes compared to HD PB lymphocytes (p < 0.05). After stimulation of PBMC in both RA patients and HD with PHA, percentages of CD2+, CD3+, CD4+, CD18+ cells significantly diminished (p < 0.05), whereas the percentages of CD54+ and CD18+ (p < 0.05) cells increased. We have found three types of RA PB lymphocytes response to complex factors in vitro: 1) the presence of the proliferative response to T-mitogens but not to r alpha 2b-IFN (56% of the patients); 2) the presence of the increased proliferative response to T-mitogens and r alpha 2b-IFN (17% of the patients); 3) the absence of the proliferative response to T-mitogens and r alpha 2b-IFN (27% of the patients). PBMC of HD demonstrate only the first type of the response. R2 alpha b-IFN demonstrated own mitogenic effect and increased mitogen-induced proliferation in PBMC cultures with a high proliferative response to T-mitogens. The levels of spontaneous and inducing apoptosis were increased in RA PB lymphocytes compared to HD. After stimulation with PHA, RA PB lymphocytes preferentially underwent apoptosis whereas cells of HD proliferated. High disease activity correlated positively with an increase of a proliferative response to mitogens and apoptosis and a decrease in the percentage of lymphocytes, expressed adhesion molecules. The treatment with r alpha 2b-IFN induces changes in T-cell response to mitogens similarly to those after incubation with r alpha 2b-IFN in vitro before treatment. CONCLUSION: Functional capacity of RA PB lymphocytes relates to the disease activity. Inhibitory or stimulatory effects of r alpha 2b-IFN depend on functional activity of RA lymphocytes. Using the test with alpha 2b-IFN incubation, we may predict changes of apoptosis and proliferation levels caused by different agents in RA lymphocytes after treatment with r alpha 2b-IFN.

Angiogenesis Inhibitors↗

[Interferon therapy effects on activation of T-lymphocytes in patients with systemic lupus erythematosus].

AIM: To elucidate the effects of combined therapy with glucocorticosteroids (GCS) and recombinant human interferon alpha or gamma (IFN) on proliferative responses of T-lymphocytes activated by various surface molecules (CD3 and CD2) in patients with SLE. MATERIALS AND METHODS: A 3-month trial entered 3 groups 15 patients each with verified SLE by APA criteria (1982). Patients of group 1, 2 and 3 received IFN-alpha (realdiron, Biofa, Lithuania) in a single dose 3 million IU i.m., IFN-gamma (inflagen, Biofa, Lithuania) in a single dose 3 million IU i.m. and cyclophosphamide in a dose 200 mg i.m. once a week, respectively. T-lymphocyte proliferative response was assessed to stimuli of two types: CD3-dependent (classic activation) and CD2-dependent (alternative activation). The analysis was made by inclusion of 3H-thymidine after 72-hour incubation of peripheral blood mononuclear cells with various stimuli. The response was assessed before the treatment, on the treatment day 20 and after the treatment. The blood from 27 donors was also examined. Flow cytometry estimated the percentage of the cells expressing molecules CD3, CD4, CD8. RESULTS: The effect is found of alpha and gamma INF on functional capacity of T-lymphocytes and on the number of cells expressing surface molecules CD3 and CD4. Realdiron produced two-phase reaction to a proliferative response to mitogenic stimuli by CD3-dependent activation pathway: the initial rise then lowering. CD2-dependent way of T-cell activation is associated with weakening of responses to all combinations of stimuli with participation of autologous red cells. This group of patients to the end of the therapy exhibited a significant decrease in the number of cells expressing CD3 and CD4 (p < 0.05 and p < 0.001, respectively). Inflagen enhanced CD3-dependent activation of T cells and normalized the response to all types of the alternative stimuli. This group demonstrated an increase in the number of cells expressing CD3 and CD4 (p < 0.01 and p < 0.05, respectively). The changes in the number of CD8+ cells in both the groups were statistically insignificant. The controls had T-cell responses reduced by both activation pathways. CONCLUSION: Preparations of both alpha and gamma interferon have a multidirectional influence on functional potential and phenotype of T-lymphocytes of SLE patients.

Adult↗

[Cell interaction in immune response].

The recognition of antigens by specific T- and B-lymphocytic receptors underlies an immune response. However, the formation of a potential signal for the activation of lymphocytes requires an additional their stimulation (costimulation). The main source of costimulation signals is the interaction of the surface molecules of lymphocytes and accessory cells. The interaction between the T-cell surface molecules CD28 and costimulatory molecules of antigen-presenting cells (CD80 or CD86) is the most important point of the T-helper cell activation. The interaction between B-cell molecule CD40 and T-helper surface molecule CD154 is the key event of B-cell (and other antigen-presenting cell) activation. When costimulation is absent, antigen recognition induces specific lymphocytic anergy or apoptosis. Defects of costimulatory molecular expression or function can cause immunodeficiency. For example, hereditary defect of CD154 expression causes the hyper-IgM syndrome. The soluble forms of some costimulatory molecules are considered to be potential immunomodulators.

Antibody Formation↗

[The classical and alternative pathways of T-lymphocyte activation in patients with systemic lupus erythematosus].

AIM: To study activation of T-lymphocytes by the CD3 (antigen-dependent) and CD2 (non-antigen-dependent) routes in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Peripheral blood mononuclears were studied in 66 patients with SLE and 27 donors. Proliferative response to activation by anti-CD3, anti-CD3+ phorbol-12-myristate-13-acetate (PMA), phytohemagglutinin (PHA), and autologous erythrocytes in combinations with PMA and recombinant interleukin-2 (rIL-2) was assessed. RESULTS: T-cell proliferation was at least two times increased under the effect of CD3 in 40.9% patients and in 100% normal subjects. Stimulation with CD3 antibodies in combination with PMA leveled the differences due to boosting of T-cell response in SLE patients. PMA alone caused mononuclear proliferation in 25% patients with SLE but not in normal subjects. Decreased response of T-cells to adhesive stimulus (autologous erythrocytes + PMA) in SLE patients was leveled by rIL-2. CONCLUSION: The proliferative response of T-lymphocytes is decreased upon stimulation with CD3 and CD2 and in some patients increased by PMA in submitogenic doses, added alone or in combination with anti-CD3.

Adult↗

[B-lymphocyte regulation of the functional activity of hematopoietic stem cells. I. The effect of activated B-lymphocytes from the murine spleen on the proliferation of syngeneic hematopoietic stem cells of the bone marrow].

The hemopoietic stem cells (HSC), obtained from the mouse bone marrow and transferred into lethally irradiated syngeneic mice, do not form colonies of hemopoietic cells in the spleen of recipients. The colony formation has been observed after transplantation of HSC together with bone marrow B-lymphocytes or precursors of T-lymphocytes (PTL), and has been mediated through soluble products of nonimmunoglobulin nature produced by B-cells. In distinction from bone marrow B-cells, the interaction of splenic B-lymphocytes with the HSC fraction does not initiate this process, but suppresses it in the presence of bone marrow PTL. The interaction of B-lymphocytes activated by LPS (in vitro) or sheep erythrocytes (in vivo) with HSC or with a mixture of HSC and PTL resulted in the formation of splenic colonies. However, the induction of colony formation has been observed only in the presence of mature T-lymphocytes (phenotype Thy-1, Sc-1), revealed as an admixture to HSC, and has been abolished after their removing in the process of fractionation of bone marrow and receiving the purified HSC fraction. It requires some membranous interaction of regulatory cells.

Animals↗

[Characteristics of the mitogenic activity of purified thymocyte growth factor].

Being purified by gel filtration and reverse phase HPLC the thymocyte growth factor from the supernatant of the cell line of intrathymic precursors of T-lymphocytes can stimulate the growth of splenocytes and thymocytes nonactivated by mitogen. Addition of suboptimal doses of mitogen or phorbol myristate acetate does not enhance the cell response to the thymocyte growth factor. The thymocyte growth factor in capable of stimulating the growth of thymocytes synergistically with interleukin-2, but the direct action of the thymocyte growth factor is not mediated by the production and reception of interleukin-2 and interleukin-4.

Animals↗

[Effects of B-lymphocytes from different organs on hemopoietic colony formation in the spleen by bone marrow cells].

The influence of B-lymphocytes from various sources on splenic colony formation was studied in the syngeneic system. B-lymphocytes were obtained by panning with IgG-fraction of rabbit anti-mouse Ig, absorbed on Petri dishes. In addition, adherent cells, Thy-1+ and SC-1+ were eliminated from the fraction of Ig(+)-cells. SC-1- and SC-1+ fractions, containing, respectively, stem cells and T-lymphocyte precursors, were obtained by panning with IgG-fraction of rabbit anti-SC-1 serum. SC-1- cells transferred to irradiated syngeneic mice did not induce colony formation in the spleen. Introduction of SC-1- and SC-1+ cells induced formation of colonies. A similar helper effect occurred when SC-1(-)-cells were introduced with bone marrow or lymph node B-cells, but not with splenic B-cells. Splenic, but not bone marrow and lymph node B-cells inhibited colony formation by combination of SC-1- and SC-1+ cells. All effects of Ig+ cells were abolished by treatment of cells with rabbit anti-MBLA serum. Thus, B-cells of various origin can either enhance or inhibit colony formation. The enhancing of inhibitory effect after B (MBLA+)-cells elimination from suspension of bone marrow and lymph node (but not spleen) Ig(+)-cells resulted from the activity of B-contrasuppressors.

Animals↗

[The relation of changes in the surface markers and the induction of thymocyte functional activity under the action of humoral thymic factors].

Mouse thymocytes were fractionated on PNA+- and PNA-cells. The PNA+-fraction was treated by tactivin--a preparation of thymic hormones. The treatment resulted in the loss of PNA-receptors from the surface of 10-12% of PNA+-cells. The treated suspension was again fractionated by the same method. PNA-thymocytes derived from both the first and the second procedure of fractionation expressed less Thy-1.2 antigen and SBA-receptors than PNA+-cells. Primary and induced PNA-thymocytes were able to produce IL-2 after mitogen stimulation. The data can be interpreted as an evidence of the ability of thymic hormones to induce not only a phenotypical but also a functional maturation of PNA+-thymocytes and of linkage of all the observed signs of maturation.

Adjuvants, Immunologic↗

[T-lymphocyte precursors--the target cells of thymocyte growth factor].

The cortisol-resistant PNA+SC- --1+Thy--1+-thymocytes are the target cells for the thymocyte growth factor (THGF), which is produced by the lines of transformed precursors of T-lymphocytes (PTL). These cells have the same properties and markers as the intrathymic PTL. The bone marrow cells do not proliferate in response to THGF but acquire that ability after the influence of thymic hormones, which induce the maturation of PTL. Thus, THGF is the autocrine growth factor of intrathymic PTL.

Animals↗

[Influence of Bacillus intermedius RNAase on thymus cell composition and T-lymphocyte differentiation in an experiment].

It was shown that exposure of mice AKR and (CBA X C57B1/6)F1 to Bacillus intermedius RNAase and its derivative selectively inactivated by the active centre histidine stimulated T-lymphocyte maturation. With using bone marrow and spleen lymphocytes of congenitally thymus-free mice it was revealed that this effect of RNAase was defined by induction of Thy-1 antigen of the lymphocyte plasmic membrane and not associated with homology of the enzyme primary structure and the alpha 1-thymosin structure.

Animals↗

[Glycosylation of glycoconjugates on thymocyte surfaces].

The ectosialation and ectogalactosylation of mouse thymocyte surface were studied. The incorporation of labeled monosaccharides (N-acetylneuraminic acid and galactose) into cell surface glycoproteins and glycolipids were demonstrated. Identification of glycolipids was carried out. The effect of glycosylation on the immune properties of thymocytes was established.

Animals↗

[Assessment of the action of taktivin on different stages of T-lymphocyte maturation].

Tactivin, the thymic hormone preparation, evokes some phenotype alterations in T-cell precursors (elimination of SC-1 antigen and expression of Thy-1-antigen) and cortical thymocytes (a decrease in the number of thymocytes carrying PNA-receptor) similar to those arising in T-cell differentiation. Tactivin induces PNA+ -thymocyte response to PHA action and increases PHA response to PNA- -thymocytes. It is weakly mitogenic for T-cell precursors and PNA- -thymocytes. The data suggest that Tactivin may be used for the treatment of immune deficiencies with T-cell differentiation and function defects.

Adjuvants, Immunologic↗

[Effect of ribonucleases on humoral immunity of experimental animals].

The stimulating effect of RNAases on the humoral immune response was observed in experiments with animals. It was shown that the stimulation was mainly mediated by the system of T-lymphocytes. In the T-lymphocyte system positive sensitivity to the enzymes was attributed to the T-helper cell subpopulation.

Animals↗

[Lines of transformed murine thymus cells. I. Production of the lines].

Supernatant of activated cells of human T-leucosis line "Jurkat" enriched with interleukin-2 (IL-2) was injected to Balb/c mice. After a number of injections the animals were sacrificed and the thymus cells were cultured in vitro. Transformed cell clones were formed on days 3-4. Two stable T-cell strains of the reproduced primary cells were obtained (TC.SC-1/1.1. and TC.SC-1/2.0). The strains corresponded to the transitional stage of pre-T-lymphocytes and consisted of tumour cells. A possible mechanism of malignant transformation of these cells is discussed.

Animals↗

[Lines of transformed mouse thymus cells. II. Cell morphology, karyology, ultrastructure and growth in vitro and in vivo].

Morphology, fine structure, karyology and growth of intrathymus pre-T-cell cultures (TC.SC-1/1.1 and TC.SC-1/2.0) were studied both in vitro and in vivo. The cultures were induced by injecting to mice a supernatant enriched with interleukin 2. The results obtained confirm the malignant transformation of cells of the lines obtained and the involvement of endogenic lymphotropic viruses in this process. The lines obtained are defective in hypoxanthine phosphoribosyltransferase. This property may serve as a basis for their use in hybridoma technology.

Animals↗

[T-lymphocyte precursor count in the thymus and the development of lymphomas in AKR/J-strain mice].

The content of T-cell precursors is increased in the thymus of AKR/J mice. Thymus also contains cells carrying markers of pre-T (SC-1-antigen) and T-(Thy-1-antigen) cells simultaneously. The level of SC-1+-cells grows just before the lymphoma appearance in the AKR/J thymus. Lymphoma cells express both SC-1 and Thy-1-antigens, i. e. they are a transitional form between pre-T- and T-cells. It is suggested that accumulation of SC-1+-Thy-1+ cells in the mouse thymus is an essential condition for the development of virus-induced lymphomas.

Animals↗