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At least 19 recordsLinked to original sources

Effect of catecholamines on lymphopoiesis in fetal mouse thymic explants.

Fetal thymic explants (14 days of gestation) from Balb/c mice were grown in organ culture for up to 12 days and the pattern of lymphopoiesis was monitored by 125IUdR incorporation and cell yields of such lobes in the presence of adrenergic agents. It was observed that, after 3 days of cultures, phenylephrine stimulated lymphopoiesis in thymic explants, whereas some inhibition was observed with isoproterenol. These observations were confirmed by autoradiography. It was also observed that cells obtained from phenylephrine-treated cultures had greater mitogen reactivity than either control (untreated) or isoproterenol-treated cultures. The possible role of cyclic nucleotides as intracellular mediators of thymocyte maturation is discussed.

Animals

[The influence of cytostatic and immunosuppressive methyl hydrazones on myelo- and lymphopoiesis in vitro (author's transl)].

The cytostatic and immunosuppressive N'-methyl-N'-beta-chloroethylbenzaldehyde hydrazones B1 and B2 inhibit the colony growth of mouse bone marrow cells and PHA-stimulated human lymphocytes in vitro in a dose-dependent manner. In the presence of B1, however, in contrast to B2, the inhibition of 3H-thymidine (3H-Tdr) uptake by the bone marrow cells and lymphocytes is insignificant. Two further benzaldehydrazones CyB4 and EB4 show little or no influence both on clony growth and nucleoside uptake. On the other hand, CyB4 inhibits the 3H-Tdr uptake by ConA- or LPS-stimulated mouse spleen cells to a gretaer degree than does B1 or B2, although CyB4 unlike B1 or B2 does not display any immunosuppressive effects in the mouse. These findings demonstrate that the 3H-Tdr method is less sensitive than the colony assays and is hence only of limited value as a measure of the vitro proliferation of mammalian cells treated with cytostatics.

Animals

[Further purification of a tissue specific inhibitor in lymphopoiesis (lymphocyte chalone?) (author's transl)].

A partially purified calf spleen extract, which exhibits the properties of a lymphocyte chalone (tissue-specific, species non-specific, non-toxic and reversible acting, endogenous inhibitor of cell proliferation) as concerning biological activities, has been described earlier. This fraction has been further purified by ion exchange chromatography with DEAE-Sephacel to a 10,000-fold purification. The most active fraction inhibited 3H-thymidine incorporation into phytohemagglutinin- or pokeweed-mitogen-stimulated lymphocytes by 86% resp. 70%, when given in a concentration of 100 ng/ml. Ehrlich-ascites-cells were not inhibited by the same concentration. The inhibiting activity is compared to other published lymphocyte inhibitors.

Animals

Recent studies on the role of the thymus in early stages of lymphopoiesis and immune differentiation.

The influence of thymus deprivation and thymus restoration was studied: a) on the cycling capacity of colony forming cells (CFU-S) in the bone marrow and b) on the establishment of tolerance in liver radiation chimeras. After neonatal thymectomy a reduction in the number of CFU-S in the bone marrow was observed. This reduction was accompanied by a striking decrease in the proportion of cycling cells in the bone marrow of thymus deprived mice. On the other hand, restoration of thymus function by thymic hormone (THF), by implantation of thymus in semi-impermeable cellophane bags, or by pregnancy, raised the number of cycling cells in the bone marrow to that of normal controls. Parental embryonic liver cells reconstitute lethally irradiated mice, and permit establishment of tolerance to further challenges of immunocompetent cells syngeneic to liver donors. We found here that adult thymectomy prevents the establishment of permanent tolerance in liver chimeras. Again, restoration of thymic function by THF permitted liver chimeric mice to resist the immunologic attack of parental spleen lymphocytes syngeneic to donor liver cells.

Age Factors

[Age and changes in the splenic lymphoid tissue of germ-free rats during the postnatal period of ontogenesis].

In germfree rats the splenic lymphopoiesis is not demonstrated by the investigation to be suppressed, and lymphoid follicules undergo age changes. Up to 15 days, periarterial zone of T-lymphocytes, responsible for cell immunity, is determined, and by the 30th day, as in control animals, peripheral zone of B-lymphocytes, responsible for hormonal immunity, is distinctly observed. In 4-month-old germfree animals, a large amount of free iron crystals is detected in the spleen, while in the organ of control animals its amount is still small. In 10-month-old germfree rats, with the appearance of reactive centers, the zone of B-lymphocytes widens in lymphoid follicules and iron crystals integrate in the red pulp. Lymphopoiesis in the spleen of the germfree rats seems to be maintained by certain local conditions which are connected with increased haemolytic function of the organ. This produces a discharge of a large amount of the products of erythrocytosis which, like autoantigens, stimulate lymphopoiesis in the spleen even when microflora is absent in the organism, while lymphopoiesis in lymph nodes in germfree animals is sharply inhibited.

Aging

Distribution and consequences of cell suspensions following intralymphatic infusion.

The fate and consequences of intralymphatic injections of cells was investigated in dogs. The distribution of intact radiolabeled cells was determined in vivo by whole body gamma scanning. Comparison of distributions resulting from intralymphatic, subcutaneous, intradermal and intravenous routes of administration showed that the distribution and duration of radiolabel in various organs varied with the route of administration. Following intralymphatic injection, radiolabel was concentrated in first echelon lymph nodes draining the site of injection and was retained in these nodes for over 4 weeks. Histologic studies showed intense cortical and paracortical lymphopoiesis to be associated with the retention of intralymphatically injected tumor cells by first echelon lymph nodes. Serial histologic examination of lymph nodes from intralymphatically injected inbred beagles revealed that the consequent lymphopoiesis persisted for 5 weeks. In vitro evaluation of peripheral blood and lymph node lymphocyte cytotoxicity to the injected cells indicated that retention and nodal lymphopoiesis was associated with the development of direct lymphocyte cytotoxicity. The effects of concommitant tumor burden, cytotoxic drugs and ionizing radiation were also investigated and suggest that the therapeutic potential for use of the intralymphatic route has not yet been realized.

Animals

Progression through key stages of haemopoiesis is dependent on distinct threshold levels of c-Myb.

The c-Myb transcription factor is expressed in immature haemopoietic cells and at key stages during differentiation. Loss of the c-myb gene results in embryonic lethality because mature blood cells fail to develop, although commitment to definitive haemopoiesis occurs. We have generated a knockdown allele of c-myb, expressing low levels of the protein, which has enabled us to investigate further the involvement of c-Myb in haemopoiesis. Low levels of c-Myb are sufficient to allow progenitor expansion but, importantly, we show that progression of progenitors towards terminal differentiation is significantly altered. Suboptimal levels of c-Myb favour differentiation of macrophage and megakaryocytes, while higher levels seem to be particularly important in the control of erythropoiesis and lymphopoiesis. We provide evidence that the transition from the CFU-E to erythroblasts is critically dependent on c-Myb levels. During thymopoiesis, c-Myb appears to regulate immature cell numbers and differentiation prior to expression of CD4 and CD8. Overall, our results point to a complex involvement of c-Myb in the regulation of proliferation and commitment within the haemopoietic hierarchy.

Alleles

Normal and leukemic hemopoiesis compared.

Using colony assays for human erythropoietic (BFU-E, CFU-E) and granulopoietic (CFU-C) progenitors, normal and leukemic myelopoietic differentiation were compared; similar patterns were found in both. However, the origin of blast cells characteristic of the disease could not be established indicating the need for a direct approach to these cells. A colony assay for blast cells in acute myeloblastic leukemia is described. Blast cell colony-formation is significantly correlated with blast cell number, and the colonies contain cells of blast like morphology without differentiation markers. It is proposed that this method, taken in conjunction with results from assays of myelopoiesis and lymphopoiesis, may provide a more complete picture of leukemic differentiation. It is anticipated that such a model will be useful in devising new therapies.

Cell Survival

Organ culture studies of nude mouse thymus.

There is evidence that peripheral lymphoid organs of nude mice, born from homozygous matings, contain a small proportion of theta-positive lymphocytes indicating that nude mice may not be totally devoid of T cell function. It has been suggested that such lymphocytes may develop within the dysplastic nude thymus itself. While this suggestion receives no support from morphological studies, it has been claimed that on explanation to organ culture the developing nude thymus becomes lymphoid. In this present study we confirm the presence of theta-positive lymphocytes in peripheral lymphoid tissues of homozygous nude mice born of nude parents. However, when we have organ-cultured nude thymus, explained from homozygous nude embryos at days 13, 14, 16 and 18 of gestation, we have found no histological sign of lymphopoiesis nor have we detected any theta-positive cells in such cultured material. On the contrary, the nude thymus in vitro develops into the polycystic structure characteristic of the adult nude thymus. We conclude that the small number of theta-positive cells present in the periphery result from extrathymic differentiation.

Animals

Spontaneous and induced appearance of murine leukemia virus antigen containing cells in organ cultures of embryonic mouse thymus.

The potential of embryonic thymus organ cultures for studies on relations of endogenous MuLV, lymphoid cells and thymic microenvironment to lymphoma development were evaluated. Four main findings are reported. First, thymuses of 14-day-old CBA and AKR embryos could be maintained in organ cultures for at least 9 weeks with sustained production of lymphocytes. Lymphopoiesis in CBA and AKR thymuses were not grossly different. Secondly, an indirect immunofluorescence (IF) technique demonstrated spontaneous appearance of MuLV-antigen-containing cells in AKR, but not in CBA thymuses. Such spontaneous MuLV expression first occurred after 16 days of organ culture, thereafter infrequently and at random in individual thymus cultures. Thirdly, incubation of AKR and CBA thymuses in lymphoma extract containing AKR-type MuLV at initiation of organ cultures induced MuLV-antigen-containing cells. These were first detected after 7-14 days in culture, somewhat earlier and initially more frequently in AKR than in CBA thymuses. In the former, induction was accompanied by a clear reduction in the number of lymphocytes per thymus. Fourthly, iododeoxyuridine (IdUrd) treatment of AKR thymuses on cultute day 0, 3 or 7 decreased the number of lymphocytes per thymus and induced appearance of MuLV-antigen containing cells, assayed 8-20 days later. The IdUrd effect was most marked on day 0, and decreased sucessively on days 3 and 7. IdUrd had a much slighter effect on CBA thymuses, causing a lower reduction in cell numbers and inducing few MuLV-antigen cells. These main results clearly demonstrate the potential usefulness of the organ culture system for studied on leukemogenesis. It may be directly applied to answer several questions raised by detailed findings in our study.

Animals

Ultrastructural autoradiographic study of blast cells in the mouse thymus. Interest for radioleukemia research.

Ultrastructural autoradiographic studies of mouse thymic blast cells after H3 Tdr injection show that their fine nuclear structure is related to their position in the cell cycle. The variations in the composition of the subcapsular blast cell population during radiation-induced leukemogenesis indicate kinetic changes in thymic lymphopoiesis, which are probably due to the oncogenic process.

Animals

Hematopathology and Pathogenesis of the X-linked recessive lymphoproliferative syndrome.

Subtle immunodeficiency to infectious agents including measles virus and ten Epstein-Barr virus (EBV) has been described in the X-linked recessive lymphoproliferative syndrome. This syndrome has affected six male cousins and possibly another boy. Three brothers died of an infectious mononucleosis syndrome, in a maternal cousin agammaglobulinemia developed three years after infectious mononucleosis, and two half-brothers of the Duncan kindred died of lymphoma of the brain and intestinal tract, respectively. In three of the boys, unusual measles viral infections had developed. Paramyxovirus-like particles suggestive of measles virus were seen at necropsy in the atrophic lymphoid tissue of two boys. Also, numerous plasma cells were seen in the brains, visceral organs and the thymus glands, and thymic-dependent lymphocytes were sparse in lymph nodes and spleen. The abnormal lymphopoiesis in the syndrome probably results from a subtle immunodeficiency, and concurrent measles and EB virus infections.

Agammaglobulinemia

Experimental studies on hemopoiesis in the pronephros of Rana pipiens.

Embryogenesis of hemopoietic cell populations in the pronephros of Rana pipiens was examined during embryonic and early larval development. Differential cell counts of Wright-Giemsa-stained cell suspensions demonstrated that granulopoiesis is the predominant hemopoietic activity in the pronephros, erythropoiesis accounts for a minor component of the hemopoietic activity (less than 10%), and lymphopoiesis within the organ is negligible. Microdensitometric analysis of Feulgen-DNA stained granulocyte populations in pronephroses from larvae that had received chromosomally labeled pronephric analgen transplants between 84 and 96 h of development demonstrated that hemopoiesis in this organ is dependent on colonization by an extrinsic hemopoietic stem cell. A similar analysis of pronephric hemopoiesis in larvae which had received chromosomally labeled, presumptive ventral blood island transplants between 62 and 67 h of development, indicates that granulopoietic cells are not derived from the embryonic blood islands. It is proposed that the pronephros may be the initial site of granulocyte differentiation during early embryogenesis. Although the embryonic origin of the hemopoietic stem cell is unknown, indirect evidence from this study indicates a dorsal stem cell compartment.

Animals

Congenital immunodeficiency and agranulocytosis (reticular dysgenesia).

A patient is presented who manifested the typical clinical and pathological features of congenital immunodeficiency and agranulocytosis (reticular dysgenesia). Treatment under gnotobiotic conditions enabled the measurement of immunogical parameters up to the 17th week of life with the following results: negative skin test, low response to phytohaemagglutinin, weak response in the mixed leukocyte culture and very few E rosettes. Peripheral lymphocytes and lymphocytes in the lymphatic tissues were markedly decreased. Humoral immunoglobulins and plasma cells in the organs were decreased. The in vitro culture of hemopoietic cells showed a diminished content of myelopoietic progenitor cells ("committed stem cells"). It is concluded that the disease may be primarily a defect of stem cells with regard to differentiation in myelopoiesis or lymphopoiesis.

Agranulocytosis