Participation of phytohemagglutinin-transformed mouse lymphocytes in development of the "graft-versus-host" reaction]

Transformed lymphocytes obtained as a result of phytohemagglutinin-stimulation of the cells of the lymph nodes of the CBA mice were incapable of realizing the graft-versus-host reaction in administration to the sublethally irradiated (CBAXC57BL/6) F1 hybrids. In this case the graft-versus-host reaction is induced by small untransformed lymphocytes with the same concentration of surface antigens detected by the antilymphocytic serum as in the intact lymphocytes.     

Immunocompetent lymphoi- cells from pregnant mice studied in the graft-versus-host reaction]

The capacity of lymphoid cells taken from C57BL/6 mice gravid from the CBA males (the second trimester) to induce the graft-versus-host reaction in the hybrids (CBA X C57B/6) F1 was reduced as compared with the cells of the virgin donors and syngeneic gravid mice. This was expressed by the prolonged survival of the experimental recipients and reduced inhibition of endogenous colony formation in the spleen of the sublethally irradiated (500 r) hybrids. At the end of gravidity this capacity was restored, in some instances even exceeding control figures.     

Suppression of interferon synthesis during the "graft-versus-host" reaction in F1(CBAXC57BL/6) mice]

The development of the graft-versus-host reaction (GVHR) in the F1(1CBA X C57BL/6 hybrid mice after the transplantation of spleen cells from the C57BL/6 parent donor resulted in a strong inhibition of the serum interferon production induced by the intraperitoneal injection of the Newcastle disease virus. In vitro with the mouse bone marrow cells during the development of the GVHR the interferon response was first reduced and then disappeared completely. The described phenomenon could therefore serve as an index of the development of the GVHR.     

Lymph node cell responsiveness in BALB/c mice infected with Leishmania mexicana

In the present study we measured the blastogenic response of lymph node cells from BALB/c mice infected with Leishmania mexicana throughout the course of infection. Results showed that infected mice displayed normal blastogenic responses in the lymph nodes until twenty weeks of infection. Thereafter, there was a gradual suppression. Comparison of the immunoresponsiveness in the spleen and lymph nodes, revealed normal responses in the lymph nodes several weeks after suppression in the spleen had occurred. Suppression of blastogenic responses in the lymph nodes was related to an adherent macrophage-like cell which actively suppressed normal proliferative responses to mitogens.     

Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice.

The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.     

Lymph node hyalinization in elderly Japanese

Lymph node hyalinization has been comprehensively investigated using specimens obtained from elderly Japanese and white Americans. Onion-peel lesions and associated meshwork areas were often found in the medullary sinus of the thoracic node (mediastinal-type hyalinization), while eosinophilic, glassy and spotty lesions were consistently seen in B lymphocyte areas of the pelvic node (pelvic-type hyalinization). The mediastinal-type hyalinization was comprised of thin collagen fibrils (ca 50 nm in diameter), whereas the pelvic-type hyalinization had thick fibrils (ca 150 nm in diameter). This difference seemed to be consistent with a difference in composite collagen fibrils of vascular walls between the thoracic and pelvic regions. The pelvic-type hyalinization was often or sometimes seen in other nodes, such as cervical, axillary, abdominal and inguinal nodes, especially in white Americans. The mediastinal-type hyalinization, usually in combination with a sinus filled with anthracotic macrophages, tended to be observed in Japanese more frequently than in white Americans. Anthracosis seemed to be connected to the pathogenesis of the hyalinization. On the other hand, because the lesion was weakly positive for Factor VIII immunohistochemistry and because lesions were located along thin vessels, the pelvic-type hyalinization seemed to originate from vascular degeneration in the nodal cortex. Due to the high incidence and large proportion in total volume of the node, the hyalinization seems to be one of the major events that diminish the nodal filtration function and ruin the node with aging.     

Hematopoietic factors in graft-versus-host reaction

Graft-versus-host (GVH) reaction has a curious unsolved area in the immunopathogenesis and pathophysiology of the immunohematopoietic system, and GVH disease remains one of the major obstacles in clinical allogeneic bone marrow transplantation. T lymphocytes and T lymphocyte subpopulations are now recognized to be initiators of this GVH reaction and disease. Also, T lymphocytes are known to be accessory cells in the regulation of hematopoiesis, and produce a variety of lymphokines relevant to hematopoiesis. Admittedly, remarkable hematopoietic changes can be found in GVH reaction, but the cellular mechanisms underlying these changes are so complex they have yet to be fully elucidated. In fact, elevated serum levels of myeloid and erythroid colony-stimulating activities were found in mice suffering from GVH disease in which marked granulopoiesis and suppression of erythropoietic differentiation were seen. In addition, each granulocyte/macrophage colony-stimulating factor (GM-CSF) or burst-promoting activity (BPA) could be detected in sera from patients with GVH disease following allogeneic bone marrow transplantation. There seems to be at least two mechanisms involved in the control of hematopoiesis with either humoral or local environmental factor, probably via the T lymphocytes or T lymphocyte subpopulations activated by alloantigens or autologous non-T cells.     

Lymph node cell composition and DNA content in their different lymphocyte populations in mice with tumor induced by murine Moloney sarcoma virus]

The ratio of T and B lymphocytes and DNA content in population enriched by these cells were analysed in the lymph nodes of BALB/c mice with progressively growing sarcomas induced by the MSV Moloney and in untreated mice. T lymphocyte enriched fractions have a higher DNA content in comparison to fractions enriched with B lymphocytes. Sarcoma development promotes a decrease in the relative number of macronucleolar lymphocytes and simultaneous decrease of micronucleolar ones in the lymph nodes, particularly in the regional ones.     

Immunosuppressive effect of graft-versus-host reaction

GVHR was elicited in adult F₁ hybrids by iv injection of parental spleen cells. The F₁ hybrids were then immunized with θ-AKR antigen. Plaque-forming cells (PFC) producing antibodies lytic for AKR thymocytes were enumerated in spleens of experimental animals using the method of cytolysis in agar-gel. The number of PFC found in spleens of animals grafted with parental cells was significantly lower than the number in spleens of animals grafted with syngeneic cells. The degree of suppression of immune response to θ-AKR depended on: (1) the duration of GVHR at the time of immunization, (2) the parental strain and the number of parental cells grafted to evoke GVHR, and (3) the source of cells grafted. Thymus and bone marrow cells when grafted together showed a synergistic effect in suppression of the host's immune response. Immunosuppression of the response to θ-AKR seems to be a more sensitive indicator of GVHR in adult F₁ hybrids than splenomegaly, which is commonly used as a means of assessment of GVHR. The possible role of immunosuppression in the pathogenesis of GVHR is briefly discussed.     

Porta-biliary area modifications during the graft-versus-host reaction in chick embryo and rat fetus]

Our results (light and electron microscopic study) show that both in chick embryos engrafted with fowl homologous spleen cells and in rat fetuses receiving blood cells from their own mother (homologous system) histologic changes occur in porta-biliary areas consisting in paravascular infiltrates (P.V.I.), bile ducts disorganization and periportal hepatocyte alterations. These modifications are closely similar to those described in other post-natal Graft Versus Host Reaction models. Yet, in both cases, the cells of the P.V.I. are chiefly of the granulocytic serie instead of the classical lympho?d P.V.I.     

Lymph node localization of non-specific antibody-coated liposomes

Subcutaneously injected small unilamellar liposomes are drained into the lymphatics and localized in the regional lymph nodes, and thus they can be used for the detection of metastatic spread in breast cancer patients and for delivery of drugs to diseased lymph nodes (1-8). An aqueous phase marker, [125I]-polyvinylpyrrolidone, and a lipid phase marker, [3H]-cholesterol, were used to study the lymph node localization of IgG-coated liposomes injected subcutaneously into mouse and rat footpads. The results show that human immunoglobulin G (IgG) coated liposomes are rapidly removed from the site of injection and are localized in the regional lymph nodes to a greater extent than control liposomes (i.e. liposomes without IgG). Free IgG was found to inhibit the uptake of IgG-coated liposomes by the lymph nodes. The localization of IgG-coated liposomes in the regional lymph nodes is influenced by charge of the liposomes. The results presented here suggest that antibody-coated liposomes may provide a more efficient way of delivering therapeutic agents to the lymph nodes in the treatment of diseases such as breast cancer with lymph node involvement. Similarly, monoclonal antibody-coated liposomes containing lymphoscintigraphic material may improve the detection of lymph node metastases.     

Lymph node accessory cells in the immune response

Summary The immune response in the rat parathymic lymph node was studied after administration of antigen into the peritoneal cavity. Special attention was paid to the accessory cells,which might induce the response. During the induction phase of the response a heterogeneous population of non-lymphoid mononuclear cells was present in the subcapsular sinus and the cortex of the node. These cells resemble veiled cells described in skin draining lymph and interdigitating cells in the paracortex of skin draining lymph nodes, but they do not contain Birbeck granules. It is concluded that the appearance of these granules depends on the site of the exudate provocation and that the presence of the organelles in these accessory cells is not obligatory for lymphocyte stimulation.