Search

The effect of "Profetal", a preparation containing human alpha-fetoprotein, on proliferative activity and differentiation of mononuclear leukocytes isolated from donor peripheral blood was studied in cultures with serum-free media. The results suggest that human alpha-fetoprotein in effective doses stimulates proliferation and blast transformation of cultured peripheral blood mononuclear leukocytes with the formation of CD34+/CD45+ hemopoietic precursor cells. This phenomenon of ex vivo generation of hemopoietic precursor cells using human alpha-fetoprotein can be important for clinical oncology, specifically, for the development of adaptive cell therapies.

We showed for the first time that prolactin stimulates the synthesis and release of immunomodulating cytokines and lymphocyte-activating factors (e.g., interleukin-1) by peritoneal macrophages. Prolactin abolished the stress-induced inhibition of proliferation of peripheral blood lymphocytes and increased cell sensitivity to regulatory effects of interleukin-1 in the reaction of lymphocyte blast transformation. These data illustrate the mechanism of immunoprotective activity of prolactin during stress.

The effect of hydrocortisone on functional activity of peripheral blood lymphocytes in different vertebrates during ontogeny was studied by the blast transformation test. Hydrocortisone in a dose of 100 mg/kg inhibited functional activities of T and B lymphocytes in vitro stimulated by mitogens. This inhibitory effect was observed in both young and adult animals. However proliferative activity of concanavalin A-dependent blood T suppressors in rats increased, especially in adult animals (by 3.5 times). Hence, hydrocortisone produced different effects on functional activity of peripheral blood lymphocytes in the studied species, and these effects are dose- and species-dependent.

We studied the role of monocytes in the effect of myelopid and myelopeptides MP-1, MP-3, MP-5, and MP-6 on functional activity of peripheral blood lymphocytes in the reaction of blast transformation. Myelopeptides MP-1, MP-3, and MP-6 suppressed blast transformation of lymphocytes. The effect depended on the presence of monocytes in a cell culture.

The cytotoxic activity of natural killer cells against3H-uridine-labeled target cells (human erythromyeloleukosis cells K-562) and the intensity of spontaneous blast transformation are studiedin vitro in the presence of human serum γ-globulin. It is shown that spontaneous blast transformation is 49–51% due to the presence of aggregated γ-globulin, while the aggregate-free γ-globulin fraction does not induce this reaction. The cytotoxic activity of natural killer cellsin vitro declines in the presence of native γ-globulin, which is related to the influence of aggregated γ-globulin, the intensity of whose formation may increase upon a manyfold decrease in the γ-globulin content of the preparation.

Effect of synthetic analogues of atrial natriuretic factor (ANF) on proliferative response and natural cytotoxic lymphocytes of human subjects was investigated in vitro. ANF-III and ANF-IV increased blast transformation lymphocytes induced by a Con-A suboptimal dose. The increase of cells activity was comparable with the effect of interleukin-2, added at a dose of 50-100 unit/ml.

Carbohydrate-enriched components were isolated from human serum γ-globulin by chelation of associated transition metals. Similar to the initial γ-globulin preparation, these components stimulatein vitro blast transformation of human lymphocytes from healthy donors and inhibit subsequent phytomitogen-induced lymphocyte blast transformation.

There are no statistically significant differences in the stimulation index for purified lymphocytes of control mini-pigs and mini-pigs with chronic alcohol intoxication. Autologous sera of control and experimental animals strongly suppress mitogen-induced blast transformation of lymphocytes without death of these cells. There are no statistically significant intergroup differences in the absolute number (per mm3) of T lymphocytes in peripheral blood.

i. N.A. Kraskina et al., in: Problems in the Microbiology and Immunology of Infectious Diseases [in Russian], Moscow (1979), p. 29. 2. V.I. Kuvakina et al., Zh. Mikrobiol., No. 4, 63 (1974). 3. A.I. Mokrenko, in: Modern Methods of Experimental Immunology and Various Aspects of Their Application [in Russian], Moscow (1976), p. 131. 4. L.A. Pevnitskii et al., in: Proceedings of a Conference on General Immunology [in Russian], Moscow (1965), p. 128. 5. N.N. Jerne et al., Science, 140, 405 (1963). 6. D.H. Katz et al., in: The Role of Products of the Histocompatibility Gene Complex in Immune Response, D. H. Katz and B. Benacerraf, eds., New York (1976), p. 541. 7. V.J. Pasanen et al., J. Exp. Med., 149, 1227 (1979). 8. L. Yaffe et al., in: International Conference on B Lymphocytes in the Immune Response: Function, Development, Interactive Properties, New York (1979), p. 112.

The immunologic activity of lymph cells obtained in the course of therapeutic drainage of the thoracic duct was studied in 14 patients with subhepatic jaundice of varied genesis. The blast transformation of lymphocytes reaction showed that lymphocytes from lymph are capable of blast formation when exposed to the action of phytohemagglutinin, antilymphocytic γ-globulin, and certain bacterial antigens. The highest intensity of the reaction was found in cultures of lymph lymphocytes taken for these purposes on the 2nd–3rd days after the beginning of lymph drainage. In the course of lymphorrhea the ability of stimulated lymph cells to undergo blast formation is reduced. In the period of lymph drainage, no blast formation takes place in stimulated cultures of patients' blood cells. The majority of antigen-sensitive lymphocytes is thus in a reserve state in the lymphoid tissue of the body.

Inhibition of blast-transformation of human lymphocytes, induced by phytohemagglutinin (PHA), with the aid of F(ab′)2-fragment of rabbit IgG was studied. Preincubation of lymphocytes with F(ab′)2-fragments for 24 h at 37 and 4°C followed by change of medium and the addition of PHA did not affect the intensity of blast transformation. However, the F(ab′)2-fragment could depress blast-transformation of lymphocytes if removed from the medium 24 and 48 h after the beginning of stimulation. It can be concluded from these results that the F(ab′)2-fragment interacts only with cells activated by the phytomitogen and exhibits its inhibitory action on cells already bound with PHA.

A mixture of bone marrow cells and lymph gland lymphocytes of C57BL mice was injected intravenously into F1 (A×C57BL) mice irradiated in a dose of 850 R. Under the influence of syngeneic lymphocytes of the C57BL mice colony-forming cells (CFUs) of the bone marrow proliferated in the F1 mouse hybrids as if they had been in a syngeneic organism. Besides restoration of the number of CFUs capable of forming colonies in a genetically foreign organism, under the influence of lymphocytes the colonies changed their direction of differentiation, with an increase in the number of granulocyte colonies. This process was accompanied by the development of a blast transformation reaction and by hyperplasia of the lymphoid tissue of the recipients' spleens.

Effect of preinjection of splenin to tuberculosis-infected guinea-pigs on the development of tuberculin shock and Bordet's phenomenon was examined. In animals exposed to tuberculin shock, splenin was found to increase blast transformation of lymphocytes in response to tuberculin, as well as the degree of the proliferative reactions in lymphoid organs. It was also demonstrated that administration of splenin led to the reduction of the complement titer and the foci of tuberculosis in the organs. In guinea-pigs with the induced Bordet's phenomenon, splenin exerted no beneficial immunomodulating effect, promoting the development of more severe tuberculous lesions in the internal organs.

Preliminary incubation of lymphocytes in a leukocyte suspension or isolated in a Verografin-Ficoll gradient at 37°C leads to more intensive blast transformation in response to stimulation by phytohemagglutinin (PHA). Preincubation in the presence of soy trypsin inhibitor (500 μg/ml) abolishes this effect. The results suggest that neutral proteinases of neutrophils or monocytes participate in modification of the response to PHA.

A decrease in the number of lymphocytes capable of responding to phytohemagglutinin (PHA) and in mixed culture was found in thymus-deficient dogs (thymectomized followed by lethal irradiation and transplantation of autologous bone marrow). On the basis of these results and the increase in the time before rejection of skin allografts in these animals, established previously, it was concluded that dogs have a population of lymphocytes of thymic origin that participate in the responses of cellular immunity and blast transformation under the influence of PHA.

Changes in humoral and cellular responses were studied during the development of allergic lesions of the myocardium in rabbits. These responses, manifestations of hypersensitivity of delayed type, are connected with transformation of cells of the active mesenchyme, responsible for the process of immunogenesis, into lymphocytes and plasma cells. In allergic lesions of the myocardium hypersensitivity of delayed type is manifested as a lympho-marcrophagal reaction in the intermuscular stroma of the heart, the thymus, and the lymph glands and also as blast transformation of the lymphocytes. A complex series of disturbances of immunologic homeostasis arises, in which the primary components are microangiopathies, blast-transformation of lymphocytes and activation of lysosomal enzymes.