Resistance of the suppressor function of T cells to agents with antiproliferative activity

Injection of cyclophosphamide (CP) in a dose of 50–400 mg/kg into mice immunized with sheep's red blood cells (SRBC) does not significantly reduce the ability of the spleen cells of these mice to suppress the primary immune response when transplanted into intact syngeneic recipients. Irradiation of the donors of immune spleen cells (ISC) in a dose of 900 R or treatment of the ISC in vitro with mitomycin C did not affect their suppressor activity. The supernatant (SN) obtained after ultracentrifugation of sonicated ISC inhibited the primary immune response of intact mice. It is concluded that the suppressor effect of ISC is due to a factor produced by the T cells; active proliferation of these cells is not essential for the realization of its action.Laboratory of Immunogenetics, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 327–330, September, 1977.     

Mechanism of tolerance toSalmonella typhi Vi antigen induced with cyclophosphamide

Treatment with Vi antigen followed after 46–48 h by cyclophosphamide induces a state of specific areactivity in mice which persists through adoptive transfer. Only trace amounts of Vi antigen were found in the blood and spleen of the tolerant mice after 2–3 weeks. No T suppressors were found in the spleen of the tolerant animals: Cells of the tolerant mice did not depress the immune response of normal lymphocytes when cultured togetherin vivo and they did not induce tolerance in intact recipients; the cells of normal donors partially restored the immunoreactivity of the tolerant animals. The results suggest that this form of tolerance is due to elimination or prolonged inactivation of the immunocompletent cells.Laboratory of Immunological Tolerance, 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 P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 440–443, April, 1977.     

Decrease of antitumor and suppressor activities of nonadherent bone marrow cells by culturing in medium conditioned with ehrlich adenocarcinoma cells

It was demonstrated that proliferation of bone marrow cells cultured in medium conditioned with tumor cells is somewhat increased. A much more potent stimulation of bone marrow cell proliferation is observed after the removal of cells carrying the erythroblast antigen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. N ^o 5, pp. 514–517, May, 1994 Presented by N. V. Vasil'ev, Member of the Russian Academy of Medical Sciences     

Comparative study of antitumor cytostatic and natural suppressor activity of bone marrow cells

Cells remaining after removal from bone marrow population of cells aggregated by wheat rudiment agglutinin retained the capacity to inhibit the growth of P815 mastocytoma and L1210 lymphoma cellsin vitro, while their capacity to suppress concanavalin-induced lymphoblastogenesis dropped. Contrary to antiproliferative activity of bone marrow natural suppressor cells, their natural antitumor cytostatic activity did not depend on the presence of interferon-γ in the medium and was not mediated by nitric oxide. Thus, bone marrow antitumor cytostatic effectors are probably not equivalent to bone marrow natural suppresser cells by cell composition and by the mechanism of antiproliferative effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 4, pp. 437–439, April, 1998     

Antibody-forming capacity of mouse spleen cells after hypoxic hypoxia and injection of erythropoietin

The absolute and relative (per 10⁶ spleen cells) number of antibody-forming cells (AFC) in the spleen of CBA mice was found to be reduced by half of the 1st, 4th, and 7th days after acute hypoxia (12 h, 6700 m) and on the 1st and 4th days after the end of exposure to chronic hypoxia (16 h daily for 16 days, 6700 m). By the 7th day after the end of exposure to chronic hypoxia the number of AFC in the spleen of the mice was back to normal. One of two injections of erythropoietin reduced the absolute and relative number of AFC in the spleen of the posthypoxic mice by 33–50% compared with control animals.Laboratory of Regulation of Immunopoiesis, Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 565–567, May, 1978.     

Suppressive activity of bone marrow cells from patients with stomach cancer. Effect of prostaglandins, transforming growth factor-β, and nitric oxide

It is shown that nonadhesive bone marrow cells from patients with stomach cancer suppress phytohemagglutinin-stimulated proliferation of peripheral blood lymphocytes of healthy donors and proliferation of Molt-4-human lymphoma cellsin vitro. Suppressive activity of bone marrow cells from cancer patients is not mediated through prostaglandin secretion, since indomethacin has no effect on it. Addition of neutralizing monoclonal antibodies to transforming growth factor-2₁, 2₂, and 2₃ partially reduces this suppressive effect. Suppressive effect of bone marrow cells from patients with stomach cancer is partially mediated through production of nitric oxide, since the inhibitor of its synthesis N⁹-monomethyl-L-arginine diminishes the inhibiting effect of bone marrow cells from cancer patients on phytohemagglutinin-stimulated proliferation of peripheral blood T cells from healthy donors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 217–220, February, 1998     

Effect of thymectomy on formation of immunologic tolerance in delayed-type hypersensitivity effectors

The effect of thymectomy on the formation of tolerance of delayed-type hypersensitivity (DTH) to sheep's red blood cells was investigated. If tolerance was induced by combined injection of a massive dose of antigen and cyclophosphamide, thymectomy did not prevent this process and prolonged the state of tolerance. If area activity was induced by a massive dose of antigen alone, thymectomy restored the ability to form DTH and prevented the formation of suppressor cells. Thymetome weakened DTH formation somewhat in intact animals, but not in animals receiving cyclophosphamide. The results confirm views regarding the diversity of the mechanism of tolerance (clonal-deficiency and suppressor). It is also suggested that among DTH effectors and their precursors there are two subpopulations which differ in their sensitivity to cyclophosphamide and thymectomy.Laboratory of Immunologic Tolerance, 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 P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 434–437, October, 1979.     

Role of interferon-γ in regulation of antiproliferative activity of bone marrow nonadherent cells

Bone marrow nonadherent cells were cultured for 3 days with supernatants of concanavalin A-stimulated splenocytes containing interferon-γ, whose activity was estimated by the ability to induced NO production. Supernatants with a high inducing activity decreased natural suppressor activity of bone marrow nonadherent cells and production of NO, but the activity of the supernatant of these cells increased. Inhibition of NO production during treatment with these supernatants prevented the decrease in suppressor activity; production of NO then increased. Supernatants with a low inducing activity increased natural suppressor activity of bone marrow nonadherent cells but not NO production. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 677–680, December, 1999     

Comparison of insulin-binding activity of blood cells in diabetes mellitus in pregnant women

Insulin-binding activity of blood cells in pregnant women is shown to vary considerably in health and in diabetes mellitus with different forms and stages of compensation. More stable changes were observed just in erythrocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 461–464, May, 1994 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Deliberate modification of the specific activity of leukemic cells

A comparative study was made of the efficacy of various types of deliberate modification of the leukemogenic activity of a transplantable line of bone marrow cells obtained from animals infected with Rauscher leukemia virus. Treatment of the leukemic cells with neuraminidase, or culturing them at a supraoptimal temperature led to complete loss of their leukemogenic activity, as shown by survival of 100% of the experimental animals and the absence of splenomegaly. Meanwhile, treatment of the cells with concanavalin A and 5-bromodeoxyuridine delayed the development of splenomegaly and lowered the mortality among the recipient animals by 70 and 20%, respectively. The results suggest that these methods of action on leukemogenic cells can be used in order to obtain material for subsequent immunization.Department of Virology, 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. D. Solov'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 448–449, April, 1977.     

Synthesis of nonspecific immunoglobulins in tolerant animals

Immunization of mice with sheep's red cells leads not only to antibody synthesis, but also to a sharp increase in the formation of nonspecific immunoglobulins. Injection of antigen into tolerant animals does not stimulte the synthesis of nonspecific immunoglobulins.Laboratory of Chemistry and Biosynthesis of Antibodies, Laboratory of Immunologic Tolerance, 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 P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 190–191, February, 1977.     

Antitumor activity of normal bone marrow cells

After separation of normal murine bone marrow cells in a Percoll density gradient cellular fractions with densities of 1.076 and 1.060 g/ml are capable of suppressing thein vitro growth of leukemia cells. The cytostatic activity of these fractions, however, does not surpass the level of antitumor antiproliferative activity intrinsic to intact bone marrow cells. These cells were found to be capable of joining the splenocytes, thymocytes, and lymph node cells in effector cytostatic cooperation and thus enhance the final antitumor effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 181–183, August, 1995     

Differential induction of natural suppressor activity of bone marrow cellsin vitro by different types of tumors

The suppressor activity of bone marrow cells not adhering to plastic is shown to appreciably increase after their 48-hour joint preincubation with mastocytoma P-815 supernatant or WEHI-3 myelomonocytic strain and to be unchanged after incubation with dupernatants of K-2 erythroleukemic strain or Ehrlich's ascitic carcinoma. P-815, WEHI-3, and K-2 tumors are shown to produce factors characterized by colony-stimulating activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 184–187, August, 1995 Presented by N. V. Vasil'ev, Member of the Russian Academy of Medical Sciences     

Electrophoretic and immunological characteristics of Fc+ and Fc− fractions of cba mouse spleen cells

Conditions for effective separation of Fc⁺ and Fc^– cells on a monolayer of sheep's erythrocytes, sensitized with antierythrocytic antibodies, were chosen. A modification of the method, consisting of replacing the poly-L-lysine by protamine sulfate, is suggested. The electrophoretic distribution profiles of Fc⁺ and Fc^– cells of the mouse spleen were established. The Fc⁺ cells mainly have low electrophoretic mobility, whereas that of the Fc^– cells is higher. The Fc⁺ fraction contains mainly B lymphocytes, the Fc^– fraction mainly T cells. The electrophoretic profiles of the Fc⁺ and Fc^– cells overlap considerably. If spleen cells are cells which do not adhere to the glass overlap to a much lesser degree.Laboratory of Cytochemistry and Molecular Biology of Immunogenesis, 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. 84, No. 10, pp. 451–454, October, 1977.     

Death of adherent spleen cells (macrophages)in vitro in hypersensitivity of delayed type to microbial antigens

The cytotoxic action of immune lymphocytes on adherent spleen cells obtained from unsensitized guinea pigs or guinea pigs sensitized with BCG was studied in autologous and allogeneic systems. The low cytotoxic effect found during culture of a suspension of spleen cells of sensitized guinea pigs with tuberculin was greatly increased after the addition of lymph node cells obtained from the same animal. Determination of death of adherent spleen cells, as also of adherent lymph node cells, can be used as a sensitive method for the detection of hypersensitivity of delayed type. The use of spleen cells as target cells is more convenient, for there are many more adherent cells in the spleen than in a suspension of lymph node cells.Laboratory of Streptococcal Infections, 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 P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 577–579, May, 1978.     

Involvement of fibronectin and interacting serum components in the regulation of activity of human natural killer cells

The cytotoxic activity of natural killer cells and the intensity of conjugate formation are studiedin vitro in the natural cytotoxicity reaction against³H-uridine-labeled human erythromyeloleukotic cells K-562 in the presence of fibronectin, γ-globulin, and fibronectin/γ-globulin combination. It is demonstrated that fibronectin does not change natural cytotoxicity, γ-globulin increases the activity of human natural killer cells, and the fibronectin — γ-globulin combination increases both the intensity of conjugate formation and the cytotoxic activity of natural killer cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 54–59, July, 1994     

Functional activity of hemopoietic and stromal cells in various types of myelodysplastic syndrome

Using clonal methods for assessment of hemopoietic and stromal cells and long-term bone marrow cell cultures, we have demonstrated heterogeneity of myelodysplastic syndrome. Low content of stromal precursor cells in native bone marrow, peculiarities in the formation of the stromal layer and its hemopoiesis-stimulating capacity in long-term cultures, and altered properties of stromal precursor cells in long-term cultures indicate defect in the stromal microenvironment in myelodysplastic syndrome. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 14–18, January, 1999     

Suppression of antibody formation by bone marrow T cells activated by histocompatibility antigens

The suppressive action of bone marrow T cells activated by histocompatibility antigens on antibody formation was studied. The bone marrow of CBA mice was shown to contain thymus-dependent lymphocytes which, on hyperactivation by repeated transplantation into F₁ recipients, have a suppressive action on the development of the cooperative immune response to sheep's red cells. Preliminary treatment of the bone marrow cells with antithymocytic globulin and complement abolished the suppressive effect.Institute of Biophysics, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Sciences of the USSR, P. D. Gorizontov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 300–302, March, 1977.     

Role of E-type prostaglandins in tumor cells during contact with NK cellsin vitro

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, N ^o 2, pp. 193–194, February, 1993