Ultrastructure of conjugates of cytolytic T lymphocytes and target cells

Conjugates of target cells and cytolytic T lymphocytes, isolated on the 11th day after alloimmunization, were investigated. Conjugates were formed by small and medium-sized lymphocytes, in the cytoplasm of which mature secretory granules, crystalloid structures, and lipids were found. The lymphocyte was spherical in shape and its area of contact with the target cell did not exceed 5–15%. Cytolysis of the target cells was observed after incubation for 30–60 min. The lymphocyte became flatter, its nucleus became oval in shape, and the area of its contact with the target cell increased. Meanwhile, hypertrophy and a change in the orientation of the Golgi complex were found in the zone of contact with the target cell, fusion of the secretory granules with the lipids and crystalloid structures took place, and immature secretory granules and vacuolar degeneration of the mitochondria appeared. Peeling of the lymphocyte membrane was observed, and structures connected with it and called membranosomes are described. It is suggested that secretory processes are activated in the cytoplasm of cytolytic T lymphocytes during their interaction with target cells.Laboratory of Systemic Blood Diseases, Oncologic Scientific Center, Academy of Medical Sciences of the USSR. Department of Electron Microscopy, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. M. Zhdanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 560–565, May, 1978.     

Effect of antiserotonin antibodies on functional activity of T and B lymphocytes and peritoneal macrophages

Experiments on C57Bl/6 mice showed that antiserotonin antibodies injected intraperitoneally in a dose of 25 mg/kg or added to cell culture in a dose of 10⁻⁷ mol/ml suppress lymphocyte proliferative response to pokeweed mitogen and stimulate functional activity of macrophages. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 140–142, February, 1998     

Formation of T lymphocytes inactivating allogeneic stem cells in the course of macrophage-thymocyte interaction

Allogeneic stem cells interact with T lymphocytes which are formed when intact thymocytes are cultured with syngeneic mononuclear phagocytes. The capacity of these T cells to inhibit the colony-stimulating activity of stem elements in endo- and exocolony formation tests is demonstrated. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 298–300, March, 1996 Presented by N. N. Trapeznikov, Member of the Russian Academy of Medical Sciences     

Induction of cytotoxic T lymphocytes specific to the molecule of the class I major histocompatibility complex for subcutaneous immunization in pads

T lymphocytes from immune lymph nodes, specific to the molecule of the class I major histocompatibility complex, were found to contain cytotoxic T lymphocyte precursors which mature to become effector cytotoxic T lymphocytes only in the presence of helper cells and L3T4⁺, but not Lyt2⁺ T helpers. The findings indicate that a subcutaneous injection of alloantigen of the class I major histocompatibility complex for immunization in the pads leads to the creaction of the type of microenvironment of the lymph nodes which prevents activation of Lyt2⁺ T helpers or leads to the activation of their functionally negligible part. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 190–193, February, 1995 Presented by N. N. Trapeznikov, Member of the Russian Academy of Medical Sciences     

Activated lymphocytes produce mediators potentiating the antitumor cytostatic activity of bone marrow cells

Mitogen-activated murine T and B lymphocytes produce soluble mediators that potentiate the inhibitory effect of bone marrow cells on the growth of leukemic cellsin vitro. γ-Interferon is a T-cell product increasing the cytostatic activity of bone marrow cells. An increase in the cytostatic activity under the effect of T-cell soluble mediators was characteristic of bone marrow cells fromnude mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 63–65, January, 1999     

Role of nitric oxide in activation of human T lymphocytes induced by bacterial superantigen

The involvement of nitric oxide (NO) in the regulation of human T cell response to bacterial superantigen (staphylococcal enterotoxin B) was studied. It was shown that stimulated T lymphocytes are the main source of NO. This superantigen markedly increased NO production and triggered the proliferative response of mononuclear cells from healthy individuals; the degree of apoptosis was low. In patients with purulent surgical diseases with high spontaneous and induced NO production, superantigen enhanced apoptosis of lymphocytes and induced anergy of T cells to enterotoxins. Increasing the concentration of NO in cultured cells from healthy individuals in the presence of NO donors also stimulated apoptosis and inhibited proliferative activity. These data suggest that NO regulates T lymphocyte response to superantigens. The increased production of NO probably contributes to the development of immunosuppression during bacterial infection. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 402–406, September, 2000     

Proliferation and cytotoxicity of thymus lymphocytes in vitro

The proliferative and cytolytic activity of lymphocytes from the spleen and intact thymus was compared after alloimmunization. The number of living cells and of DNA-synthesizing cells in a monoculture of thymocytes was 90–97% less, and in a mixed culture of thymus cells about 80% less that the corresponding number of spleen cells. The index of stimulation of immune thymocytes was several times greater than that of immune spleen cells. The peak of cytotoxicity was observed on the fourth to fifth day of stimulation, when the cytolytic activity of the immune thymocytes was close to the activity of immune spleen cells. The low DNA synthesis and the considerable cytotoxic activity of the immune thymocytes mean that stimulation of thymus cells in vitro can be used to obtain a cell population with a high content of cytolytic T lymphocytes.Laboratory of Systemic Blood Diseases, Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. V. Baroyan.) Translated from Byulleten Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 330–333, September, 1977.     

Thymectomy and splenectomy in adult mice do not affect suppressor activity of T lymphocytes specific for antigens of the H-2 complex

Laboratory of Mechanisms of Regulation of Immunity, Research Institute of Carcinogenesis, All-Union Oncologic Scientific Center, Academy of Medical Sciences, Moscow. (Presented by Academician N. N. Trapeznikov, Academy of Medical Sciences.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 4, pp. 392–395, April. 1992.     

T lymphocytes that infiltrate nasal polyps have a specialized phenotype and produce a mixed TH1 /TH2 pattern of cytokines

Background: Nasal polyps (NPs) are inflammatory reactions in the nasal mucosa the etiology and pathogenesis of which remains unknown. Objective: The purpose of this study was to study in detail the phenotype and function of T lymphocytes infiltrating NPs by analyzing the expression of surface markers and cytokine secretion. Methods: NP tissue samples and peripheral blood were obtained from 18 patients. Mononuclear cells were purified from these samples, and their phenotype was investigated by triple-color immunofluorescence and flow cytometric analysis. Cytokine production was determined in cultures by using an ELISA technique. Results: NP lymphoid cells mainly consisted of T lymphocytes. These T lymphocytes showed a CD45RO+CD45RA– phenotype and expressed pan-T cell molecules; the CD8+ subset was predominant. NP T cells showed a lower density of CD28, CD3, and TCR-αβ compared with T cells from peripheral blood. NP T lymphocytes expressed the activation markers DR and CD69 and exhibited the adhesion molecule profile CD54+, CD62L–, and CD103+ CD49d^low . Virtually all NP T cells bore CD95 (FAS), but they did not undergo apoptosis, either spontaneously or induced by CD95 cross-linking with the mAb CH11. The pattern of cytokines secreted by NP T lymphocytes was characterized by the spontaneous and simultaneous production of IFN-γ and IL-5. Neither IL-2 nor IL-4 were detectable in nonstimulated cultures. Conclusion: This study defines the T lymphocytes that infiltrate NPs as memory T cells in an activated status, with homing properties related to the mucosal immune system. They are resistant to anti-CD95-mediated apoptosis and produced a mixed T_H1 /T_H2 cytokine pattern as defined by the simultaneous production of IFN-γ and IL-5. (J Allergy Clin Immunol 1998;102:953-60.)     

Electron microscopic examination of the interaction between human erythrocytes and liposomes containing DC-Cholesterol

Human erythrocytes treated with cationic liposomes containing DOPC/DC cholesterol (2∶3 mol/mol) or DOPE/DC cholesterol (2∶3 mol/mol) are studied by electron microcopy. DOPE-containing liposomes exhibit a markedly greater ability to interact with the erythrocyte surface and to initiate a mosaic structure represented by smooth and rough surfaces on freeze-fractures of the erythrocyte plasma membrane. The interaction between DOPE/DC-cholesterol-containing liposomes and the plasma membrane provides the basis for using these liposomes to deliver DNA into the cell cytoplasm. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 83–86, July, 1996     

Light-optical and electron-microscopic study of alveolar brush cells of the rat lung

In semithin sections through rat lung tissue stained metachromatically with toluidine blue 52 alveolar brush cells (ABC) were discovered. During a light-optical study the distinguishing features of these cells were the pyramidal shape of their body, the basal position of the nucleus, the darker staining of the cytoplasm than in other alveolar cells, and the presence of microvilli on the small free surface of the cell. For every 21 type II and 15 type I alveolar cells there was one ABC. Of the total number of ABC 41.1% are located at junctions between neighboring alveolar cells, 32.7% on the alveolar wall facting the cavity of one alveolus, 16.8% near the entrance to the alveoli, and 9.4% facing the lumen of two adjacent alveoli simultaneously or near Cohn's pores. Parallel electron-microscopic investigations revealed a granular cytoplasmic reticulum in ABC of an unusual type for other alveolar cells; it consisted of blocks of 5 to 8 apparently confluent tubules, bundles of fibers microtubules, and vacuoles in the apical cytoplasm. The structural organization of the ABC, their topography, and the frequency with which they were found in the alveoli of rats are evidence that these cells are chemoreceptor in nature.Laboratory of Geographic Pathology of the Baikal-Amur Trunk Railroad Zone, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 592–596, November, 1978.     

Electron-microscopic study of plasma cells from regional lymph nodes of rats after topical interferon administration

Transmission electron microscopy of plasma cells from soft strands of cranial deep cervical lymph nodes removed from male Wistar rats at different times after their intranasal treatment with an aqueous α-interferon solution showed a decreased volume of the Golgi complex and lowered numbers of ribosomes and mitochondria in both mature and immature plasma cells. The results of the study are tentatively interpreted as indicating reduced energy potentials and antigen-synthesizing capabilities of the plasma cells formedde novo after α-interferon treatment. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 60–63, July, 1996     

Cytokine-induced differentiation and proliferation of human T lymphocytesin vitro: Effects of interleukin 2 and interleukin 6

The contents of CD8⁺, CD4⁺CD8⁺, CD3⁺HLA-DR⁺, CD⁺INF-γ⁺ T cells, and natural killers (CD16⁺56⁺) and NK/T cells (CD16⁺56⁺CD3⁺) increase after 7-day culturing in the presence of interleukin-2. The number of apoptotic cells and cells in S-, and G₂+M phases of the cell cycle also increased. Interleukin-6 predominantly induced proliferation of CD3⁺HLA-DR⁺ T cells and G₂+M mitotic cells. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 129, No. 6, pp. 667–671, June, 2000     

Characterization of benzodiazepine receptors of human lymphocytes

It is demonstrated that benzodiazepine binding sites on human peripheral blood lymphocytes are the peripheral type receptors. The binding sites for the selective agonist³H-Ro 5-4864, but not for the antagonist³H-PK 11195, are completely inactivated by freezing-thawing of lymphocytes. The binding of³H-Ro 5-4864 to intact lymphocytes is activated by GABA and (+)baclofen. It is shown that the selective ligands Ro 5-4864 and PK 11195 bind to different subtypes of benzodiazepine receptors on human peripheral blood lymphocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 405–408, October, 1998     

Changes in H-alloantigen-recognition function of lymphocytes after hydrocortisone administration in mice

The ability of spleen, thymus, and bone-marrow cells of intact (control) and hydrocortisone-treated (experiment) CBA mice to induce a lymph node graft versus host reaction (GVHR) in (CBA×C57BL)F₁ hybrids was compared. After injection of hydrocortisone into the donors in a dose of 2.5 mg per mouse their spleen cells induced a more active GVHR, as shown by an increase in the lymph node indices and in the percentage of immunoblasts in the regional (popliteal) lymh node compared with the control. After transfer of thymus cells of hydrocortisone-treated donors the number of immunoblasts was higher than, but the weight of the lymph node was almost the same as in the control. Conversely, after injection of bone marrow cells from hydrocortisone-treated donors, the lymph node enlarged whereas the percentage of immunoblasts did not increase above the control. Consequently, when the increase in the hydrocortisone level is exogenous in nature, the cell populations of the spleen and thymus contain a higher proportion of T lymphocytes, which respond by proliferation to contact with H alloantigens.Institute of Clinical and Experimental Medicine, Academy of Medical Sciences of the USSR, Siberian Branch, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 10, pp. 458–459, October, 1977.     

Requirement of the T cell antigen receptor occupancy for the target cell lysis by cytolytic T lymphocytes

We have constructed a bivalent bifunctional F(ab)2 fragment with binding specificity for a V beta 8 T cell antigen receptor and human tumor-associated antigen. Using the bifunctional antibody to focus cytolytic activity of mouse CTL to a human carcinoma cell line and anti-V beta 8 TCR Fab' as a competitor, we demonstrate that only a small percentage (-0.5%) of the TCR engaging on the target molecule is sufficient to deliver a lytic signal to the target cells.     

Interaction between T and B lymphocytes and their migration in the immune response during methylcholanthrene-induced carcinogenesis

Methylcholanthrene (MC) was injected intramuscularly in a dose of 0.3 mg into (CBA×C57BL)F₁ mice and the ability of their T and B lymphocytes to cooperate during the immune response to injection of sheep's red blood cells and also migration of these cells from the thymus and bone marrow into the spleen were investigated. The results showed that the immunodepressant action of MC is connected with inhibition of processes of migration and cooperation of T and B lymphocytes in the immune response. It is concluded that the immunosuppression developing during carcinogenesis is complex in character and is realized at different stages of immunogenesis.Institute of Biophysics, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. D. Gorizontov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 10, pp. 464–466, October, 1977.     

Androstenedione conversion in human peripheral blood lymphocytes

The ability of human peripheral blood lymphocytes to convert the androgenic steroid metabolite androstenedione diminishes in women over 45 years old or during menopause. In patients with breast cancer in menopause the ability of lymphocytes to convert androstenedione is enhanced compared with the control. The intensity of conversion in circulating lymphocytes correlates with the blood concentration of sex steroids. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 517–519, May, 1994 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences