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Biomedical subjects

K Nouza

Publications and source records attributed to K Nouza.

At least 55 records · Page 3Linked to original sources

Studies about induction of resistance to the reaction of grafts against their host.

The prevention of reactions of transplanter grafts against their host (GVHR)--the most serious obstacle to transplantations of allogenic bone marrow--still remains an actual problem. The results of studies about the conditions leading to the development of and about the basis of the resistance of /B10 X A/F1 hybrid mice to the GVHR elicited by A/Ph parental spleen cells, having been induced by a previous local or systemic application of various types of parental cells, are presented in this paper. The injection of an adequate dose of A/Ph mouse thymocytes into the paws of /B10 X A/F1 hybrids leads to the development of resistance against within three days, while a similar injection of B10 thymocytes remains without effect. Systemic administration of the A/Ph thymocytes and of cells of the spleen (and also of their fractions differing from one another by their adherence to nylon cotton-wool) induces resistance towards the regional type of the GVHR of A/Ph cells only after as long as seven days; the B10 splenic cells are also effective in this manner. According to this, it appears that the regional type of resistance manifests signs of specificity while the general type of resistance is nonspecific, and also that the degree of resistance is not related to the intensity of the primary GVHR. When the nature of the resistance was analyzed it appeared that both the nylon nonadherent and the adherent fractions of spleen cells of resistant individuals were capable of transferring the inhibition upon lymphocyte of normal individuals. It was, in both cases, the T-lymphocytes which were responsible for the inhibition, as has been demonstrated by the anihilation of this inhibitory activity of the nylon wool adherent cells by a monoclonal anti Thy 1.2 antibody with a complement.

Animals↗

Immune response of mice to sarcoma I allograft studied by adoptive transfers of spleen, thymus, and lymph node cells to secondary recipients.

Thymus, spleen, and lymph node cells from different periods of Sarcoma I allograft development in untreated (Sa I) or xenogeneic antithymocyte serum-treated (ATS-Sa I) B10 mice were adoptively transferred to secondary B10 recipients. While in sublethally (4.3 Gy) irradiated recipient mice the tumor destructing activity was predominantly expressed, in untreated recipients of transferred cells it was mostly the tumor enhancing activity. Therefore, in further studies directed at the detection of tumor enhancing activity, the adoptive transfers were only performed in untreated recipients. Thymus cells both of Sa I and ATS-Sa I mice showed a tumor enhancing activity all through the followed period, with a peak between days 7 and 21, then it decreased. Also the spleen cells of both groups had a tumor enhancing effect all the time, with a peak of activity on day 7. Spleen and thymus cells of progressors enhanced the tumor growth slightly more strongly than did those of the regressors. The tumor enhancing activity of spleen cells was in the beginning period confined mainly to the polystyrene nonadherent fraction of cells, at later times, in the progressors it was manifested in the adherent as well as in the nonadherent fractions. In the population of lymph node cells, at the start of tumor regression (in Sa I mice on day 7, in ATS-Sa I mice on day 14), a tumor destructing activity was observed. In both groups this activity was at later times followed by a tumor enhancing activity. The interpretation of the tumor enhancing activity of thymus and spleen cells of Sa I and ATS-Sa I mice is complicated by the tumor enhancing activity of cells of normal mice without tumor (N).

Animals↗

Genetic resistance in the graft-versus-host reaction.

Genetic resistance (GR) of (B10 x A/Ph)F1 hybrid mice to parental B10 grafts limits the 'performance' of both hemopoietic and lymphoid cells. In comparison with A/Ph spleen cells, B10 cells induce only a slight regional graft-versus-host (GVH) reaction and a delayed systemic GVH reaction. The GR to lymphoid cells is not sensitive to total body irradiation, to cyclophosphamide, or to various xenogeneic sera (e.g. antilymphocyte, antimacrophage, antithymocyte). A high dose of antimarrow serum was partially effective, but the most suppressive effect was obtained by treatment with silica. Besides some similar features, GR action on hemopoietic and lymphoid cells revealed several differences and the nature of these is discussed.

Animals↗

Study of destructive mechanisms of the immune response to sarcoma I allograft in mice.

In B10 mice (H-2b) the Sarcoma I allograft (H-2a) was after a period of temporary progression definitely rejected by the allo-transplantation reaction. After a treatment of B10 mice with xenogeneic antithymocyte serum (ATS) the primary growth of the Sa I allograft was enhanced, later the allograft grew either permanently or, after a short regression, exhibited secondary growth, or permanently regressed. The destructive activity of spleen cells from untreated recipients, as measured according to the Winn neutralization test, increased at the time of tumor rejection and remained elevated. In ATS-treated recipients the destructive activity was markedly suppressed during primary tumor growth, at the time of temporary regression significantly increased and in permanent regressors remained elevated. In progressors there was again a decrease of this activity. The destructive activity in the spleen of regressors was found mainly in the cell fraction which did not adhere to nylon wool; these cells significantly accelerated the development and enhanced the destructive activity of normal spleen cells. The decrease of destructive activity in recipients with progressively growing tumors was detected both in cells adhering and in those which did not adhere to nylon wool. Besides this defect, the defect of proliferative activity of spleen cells was detected by the local graft-versus-host reaction test in non-treated as well as ATS-treated recipients. It could not be directly proven that the suppression of the alloimmune reactivity was caused by suppressor cells--in spleens of progressors there were found no cells capable to suppress the activity of effector cells nor the evolution of the destructive activity of normal spleen cells.

Animals↗

Changes induced in the lymphoid system by the double-stranded RNA.

Systemic (i.p.) single injection of ds RNA, an inducer of interferon, increases significantly the weight and cellularity of the lymphoid system. The peaks of increase are evident in peritoneal lymph nodes 24 h, in popliteal, axillary and inguinal lymph nodes 48 h, in the spleen and liver 72 h post-inoculation. Thymus weight and cellularity decrease markedly (with a minimum at 24 h) and the number of peritoneal cells also decreases. The parameters examined gradually return to normal values. Local injection of the same dose of ds RNA into the hind footpad results in a marked increase in the weight of the ipsilateral popliteal lymph node and, with some delay, in an increase in its cellularity. In addition, local injection has an effect on the other lymph nodes, the spleen and thymus, even though the effect is slighter than that of systemic injection. The mechanisms by which ds RNA induces changes in the lymphoid system are discussed.

Animals↗

The role of target antigens coded by subregions of the mouse H-2 complex in the nature of growth of sarcoma I tumor allograft.

The nature of the development of tumor grafts of Sarcoma I in allogeneic mice is determined by the immunogenicity of membrane markers of tumor cells coded by the major H-2 system. Minor (non-H-2) systems fail to assert themselves in tumor transplantation. The role of various subregions of the H-2 system may already be followed in normal Sa I recipients: a more striking differentiation is achieved in hosts treated with xenogeneic antilymphocyte serum. Those presenting the strongest barrier were specificities coded by the entire region of the H-2 complex. Of the subregions of the H-2 system studied here, H-2K meant a stronger barrier to tumor growth than the H-2D region. When the tumor antigenic specificities of both H-2K and H-2D regions were extended to include also those of the H-21 regions, tumor growths were for the most part restricted; on the other hand, the inclusion in tumor antigen specificities coded by H-2KAB of the JE region specificities brought about a moderate stimulation in tumor growth. This differences in the fate of tumor allograft may be due to a quantitatively or qualitatively different development of the host's immune response against various tumor antigen specificities coded by subregions of the H-2 system or to a varying ability of the tumor grow across different barriers of the H-2 system.

Animals↗

Changes in lymphoid organs, peripheral blood and in homing of lymphocytes after administration of local anaesthetics.

The newly synthetized local anaesthetics of the carbanilate type--pentacaine and heptacaine, and the currently used trimecaine have been previously found to exhibit markedly different effects on immune reactions in vitro and in vivo when administered in equitoxic doses. These compounds are now assayed for their influence on the weight and cell count in lymphoid organs, on peripheral blood leucocyte count and homing of 51Cr-labelled syngeneic lymph node cells. We have found that the weight and cell count in the thymus, spleen, lymph nodes, bone marrow and the levels of peripheral leucocytes are reduced after administration of pentacaine, whereas heptacaine and trimecaine have no effect on these parameters. In contrast to heptacaine and trimecaine, pentacaine significantly reduces also the homing of lymph node cells to the recipients' lymph nodes and increases their homing to bone marrow.

Anesthetics, Local↗

Effect of local anaesthetics on immune reactivity.

Two local anaesthetics, pentacaine and trimecaine, were assayed for their effects on immune reactivity of mice in the regional popliteal lymph node after local injection of the antigen, on the regional graft-versus-host reaction and on the ability to reject skin allografts. These local anaesthetics exhibited a dose-dependent, immunosuppressive effect on all the systems used, although the mechanism of their action was different: pentacaine exerted a destructive effect on lymphocytes, whereas trimecaine induced a blockade of the lymphocyte functions.

Acetanilides↗

Addition of serum to the medium used for preparation of cell suspensions as a possible source of artifacts in cell-mediated reactions studied by means of the popliteal lymph node test.

Conditions for preparations of cells used in immunogenetic studies may substantially affect their properties and the results obtained. It was found that short-term incubation or a mere preparation of parental spleen cells in a medium containing either xenogeneic serum or concanavalin A (Con A) increase their ability (after footpad injection) to induce enlargement of the popliteal lymph node in (B10.LP x A/Ph)F1 hybrid recipients. Under similar conditions, enlargement of PLN could be induced also by syngenetic F1 hybrid cells. The greater lymphadenomegaly following the injection of parental or syngeneic cells prepared in serum-containing medium may be explained by the host reaction against additional foreign antigens rather than increased GVH reactivity or autoimmunity.

Animals↗

Influence of antithymocytic serum on the regenerating activity of the liver after partial hepatectomy in mice.

In experiments on mice the effect of rabbit-anti-mouse antithymocytic serum on the growth of the liver and on the onset of proliferating activity of the liver after partial hepatectomy was studied to elucidate the question of assumed participation of the lymphoid system in the proliferation of hepatic tissue. Administration of three doses of antithymocytic serum (0.1 ml/10 g) by the i.p. route in 24 hour intervals led to a marked increase of the weight of the spleen and increase of DNA synthesis in liver of non-operated mice. Administration of serum 24 hours before partial hepatectomy (PHE) concomitantly with PHE and 24 hours after PHE did not influence substantially the rate of DNA synthesis in the regenerating liver 34 and 48 hours after PHE and did not influence the mitotic index of hepatocytes. In the livers of mice to whom antithymocytic serum was administered proliferation of cells of the lymphocyte series and phagocyte activation occurred. These cells were located in the hepatic sinuses and periportal areas. Antithymocytic serum--contrary to chemical immunosuppressive substances--does not exert an inhibitory action on regeneration of hepatic tissue; alone does not even cause inhibition of the lymphoid system which could exert a negative effect on regeneration of the liver.

Animals↗

Immunosuppressive properties of the antibiotics cytostipin and vermiculine.

The properties of two antibiotics, cytostipin isolated from Penicillium stipitatum and vermiculine isolated from Penicillium vermiculatum, were examined in two systems for a rapid screening of current immunosuppressive agents [nucleolar test determining the degree of RNA synthesis in nucleoli of individual lymphocyte populations, and the reactivity of mouse lymphocytes to "T" (PHA) and "B" (LPS) mitogens]. Both antibiotics, distinctly suppressed the increase in number of "active" lymphocytes with compact nucleoli in the popliteal lymph node activated by SRBC. Incorporation of 3H-uridine into PHA-stimulated "T" lymphocytes was suppressed by both antibiotics, incorporation into LPS-stimulated "B" lymphocytes was inhibited by cytostipin but stimulated by vermiculine. The antibiotics were also tested in another two "classic" immune systems, the Jerne test and the GVH reaction. Both antibiotics in doses markedly inhibitory for GVH reaction did not suppress but significantly increased the number of the haemolytic plaques in spleens of SRBC-immunized mice.

Animals↗

Response of blood leucocytes to an intraperitoneal immunization in normal mice and leucopenic mice with the nu gene.

The response of leucocytes to an intraperitoneal injection of sheep red blood cells was investigated in normal (+/+) mice, athymic (nu/nu) mice and their hybrids (nu/+). In +/+ mice (in addition to a non-specific decrease in the number of granulocytes in the first 6 h after injection) the leucocyte levels were below the initial levels almost throughout the experiment (12 days). This was due mainly to lymphocytopenia. In nu/+ and nu/nu mice a marked leucocytosis developed, due mainly to the increased numbers of lymphocytes. The response of lymphocytes estimated by the morphological appearance of nucleoli showed an increase in numbers of both active lymphocytes with RNA-synthesizing nucleoli and terminal lymphocytes with micronucleoli.

Animals↗

Dissociation of the proliferative and effector non-H-2 minor histocompatibility-alloimmune responses.

The first-set and second-set allotransplantation reactions against skin grafts and the primary and secondary proliferative graft-versus-host reactions in the popliteal lymph nodes were compared in both directions in a non-H-2 system (mouse strain combinations C57BL/10ScSnPh (further B10) and B10.C3H(40NX) further 40NX) differing at H-1 plus H-?). While 40NX recipients gave stronger reactions against B10 antigens in the allotransplantation reactions, the situation was reversed in the GVHR, B10 cells reacting more strongly against 40NX antigens. The findings of a dissociation between the mechanisms of allotransplantation reaction adn proliferative GVHR suggest that the genetic determination of the target antigens and the reacting lymphocyte populations are more complex at the minor histocompatibility systems than has been expected.

Animals↗

Functional differentiation of mouse T lymphocytes. GVHR-precursors: tissue origin and specificity of activity inducer.

For theoretical and practical reasons, it is important to find out whether the differentiation of T cell precursors to the functional lymphocytes can be induced under in vitro conditions. Using the local GVHR assay (based on the enlargement of the popliteal lymph node), the inducibility of the precursors of reactive cells was studied with bone marrow, thymus, spleen, and lymph node cell suspensions submitted to short-term incubation with cell-free extracts from calf thymus, spleen or brain. GVHR-precursors from bone marrow were inducible not only specifically (i.e., with thymus extract) but also--and even to a higher degree--with spleen or brain extract. Thymus and spleen cell suspensions (the latter also depleted of the reactive subpopulation by treatment with anti-Thy 1.2 serum and complement) were, on the other hand, inducible mainly specifically, whereas lymph node cells were refractory to induction. The inductive action of tissue extracts obviously depends on the tissue origin of T cell precursors; their effects on pre- and postthymic differentiation of T lymphocytes are discussed.

Animals↗

Effect of immunosuppressive agents on the blastogenic response of mouse spleen T and B lymphocytes. I. Culture conditions and the evaluation system.

A microplate culture system has been standardized for blastic transformation of lymphocytes, using various mitogens more or less specific to T lymphocytes (concanavalin A, phytohaemagglutinin, erythrogenic toxin) or B lymphocytes (lipopolysaccharides and their lipids A, pokeweed mitogen). The mitogen-stimulated lymphocyte activation was examined by the use of the nucleolar test determining the state of nucleolar RNA synthesis by morphologic criteria. In this introductory paper to a series of papers analyzing the specificity of action of the various chemical and biological immunosuppressive agents on the blastogenic responses of T and B lymphocytes, optimal concentrations of cells and blastogenic substances and other parameters were tested, and the kinetics of transformation was investigated in detail.

Animals↗