Autosensitization of lymphocytes against thymus reticulum cells

Lymph nodes of normal rats contain lymphocytes that can be induced in vitro to mediate a specific cellular immune reaction against reticulum cells derived from syngeneic adult thymus glands. It is likely that these lymphocytes had access to reticulum cell antigens during the period in which they developed immunocompetence within the thymus. This suggests that contact with self-antigens during development may not eliminate self-reactive lymphocytes. These findings are in conflict with the theory that natural tolerance to self-antigens depends upon elimination of lymphocyte clones.     

Organ-resident, nonlymphoid cells suppress proliferation of autoimmune T-helper lymphocytes

Local presentation of autoantigen by organ-resident cells inappropriately expressing Ia determinants has been implicated in organ-specific autoimmunity. Experimental autoimmune uveoretinitis, induced in rats by immunization with retinal soluble antigen, is used as a model of organ-specific autoimmunity. In an in vitro system derived from this model, uveitogenic rat T-helper lymphocytes specific to the retinal soluble antigen, or control T-helper lymphocytes reactive to the purified protein derivative of tuberculin, were cocultured with Ia-expressing syngeneic retinal glial cells (Müller cells) in the presence of specific antigen. Antigen presentation was not apparent under ordinary culture conditions, and the Müller cells profoundly suppressed the proliferative response of primed T-helper lymphocytes to antigen presented on conventional antigen-presenting cells, as well as their subsequent interleukin-2 (IL-2)-dependent expansion. Suppression of proliferation was accompanied by inhibition of IL-2 production in response to antigen, as well as by reduction in high-affinity IL-2 receptor expression, and proceeded via a contact-dependent mechanism. These results suggest a role for locally acting suppression mechanisms in immune regulation and maintenance of tissue homeostasis.     

The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes

T lymphocyte chemotactic factor (TCF) was purified to homogeneity from the conditioned media of phytohemagglutinin-stimulated human blood mononuclear leukocytes by a sequence of chromatography procedures. The amino-terminal amino acid sequence of the purified TCF showed identity with neutrophil-activating protein (NAP-1). Both TCF and recombinant NAP-1 (rNAP-1) were chemotactic for neutrophils and T lymphocytes in vitro supporting the identity of TCF with NAP-1. Injection of rNAP-1 into lymphatic drainage areas of lymph nodes in Fisher rats caused accelerated emigration of only lymphocytes in high endothelial venules. Intradermal injection of rNAP-1 caused dose-dependent accumulation of neutrophils and lymphocytes.     

Norepinephrine: reversal of anorexia in rats with lateral hypothalamic damage

Injection of norepinephrine in the lateral ventricles of rats recovering from lateral hypothalamic anorexia caused immediate feeding and, frequently, overeating. Intraventricular administration of the alpha-noradrenergic blocker, phentolamine, suppressed feeding in both normal rats and rats that had recovered from lateral hypothalamic lesions. Feeding is reinforced by ascending medial forebrain bundle fibers that form alpha-noradrenergic synapses in the hypothalamus and forebrain. Damage to these fibers suppresses feeding by reducing noradrenergic transmission and, hence, the rewarding value of food. Recovery of feeding after hypothalamic lesions coincides with the recovery of noradrenergic reward function.     

Lymphocytes from thymectomized rats: immunologic, proliferative, and metabolic properties

Thoracic duct lymphocytes from neonatally thymectomized Lewis rats fail to produce runt disease in newborn Brown Norway rats when injected with up to ten times the number of normal lymphocytes needed to cause runting. The immunologically deficient lymphocytes appear, however, to confer tolerance, and at least some enlarge and divide when stimulated in vitro with phytohemagglutinin, or xenogeneic or allogeneic cells. Small lymphocytes from thymectomized animals have defective RNA metabolism as judged by a marked impairment in their ability to incorporate uridine-5-H(3) or cytidine-H(3) in vitro.     

Cell-bound immunity to autologous and syngeneic mouse tumors induced by methylcholanthrene and plastic discs

A colony-inhibition assay, was lused to demonstrate specific immunity in vitro against syngeneic mouse sarcomas induced by mlethlylcholanthrene or implanted Dictabelt plastic discs. An immunity to methylcholanthrene-induced tumors could also be demonstrated with lymphocytes derived from the autologous primary tumor-bearing host 3 to 8 days after removal of the primary tumor.     

A distinct endothelial cell recognition system that controls lymphocyte traffic into inflamed synovium

Lymphocytes are essential mediators of normal tissue inflammatory reactions and of pathologic tissue damage in, for example, rheumatoid arthritis and other autoimmune diseases. In a study of the mechanisms controlling lymphocyte entry into sites of inflammation from the blood, the function and specificity of lymphocyte-endothelial interactions were examined in inflamed joint tissue (synovium) from patients with rheumatoid arthritis. Synovial high endothelial venules (HEV) supported the binding of normal peripheral blood lymphocytes in vitro. The characteristics of this binding, which were similar to those of lymphocyte-HEV interactions controlling lymphocyte migration into organized lymphoid tissues, included a requirement for calcium ions, a dependence on metabolic activity, and a preferential adherence of circulating lymphocytes as opposed to immature thymocytes. However, the binding of lymphocytes to synovial HEV was not inhibited by a monoclonal antibody to lymphocyte receptors for lymph node HEV, and synovial HEV failed to bind either lymph node HEV-specific or mucosal HEV-specific B lymphoblastoid cells. The results suggest that a lymphocyte-endothelial cell recognition system that is distinct from such systems in organized lymphoid tissues directs the extravasation of normal lymphocytes as well as pathologically important effector cells into inflamed synovium.     

Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis

In a study of the mechanism of resistance to autoimmune disease induced by T cell vaccination, rats were vaccinated against experimental autoimmune encephalomyelitis (EAE) by injecting them once in the hind footpads with a subencephalitogenic dose (10(4)) of a clone of T lymphocytes specific for myelin basic protein (BP). The response to vaccination was assayed by challenging the rats with an encephalitogenic dose (3 X 10(6)) of T lymphocytes of this BP-specific clone. Five to six days after vaccination, the cells responsible for mediating resistance to adoptively transferred EAE were concentrated in the popliteal lymph nodes draining the vaccination site. Transfer of the draining lymph node cells to unvaccinated rats led to loss of resistance in the donor rats and acquisition of resistance by the recipient rats. Limiting-dilution cultures of the draining lymph node cells were established with irradiated cells of the BP-specific clone as stimulators. Two sets of T lymphocytes specifically responsive to the BP-specific T cells from the clone were isolated: CD4+CD8- helper and CD4-CD8+ suppressor cells. The helper T cells, like the BP antigen, specifically stimulated the BP-specific vaccinating clone. In contrast, the suppressor T cells specifically suppressed the response of the BP-specific vaccinating clone to its BP antigen. These results suggest that T cell vaccination induces resistance to autoimmune disease by activating an antiidiotypic network.     

Antigenic similarity between cells transformed by ultraviolet radiation in vitro and in vivo

Cells of the 10T 1/2 mouse fibroblast line transformed in vitro by ultraviolet radiation are antigenically similar to those from skin cancers produced in mice by repeated exposure to ultraviolet radiation. Both types of tumor cells grew preferentially in ultraviolet-irradiated syngeneic mice relative to untreated animals, and both were recognized by ultraviolet radiation-induced tumor-specific suppressor lymphocytes. These properties were not shared by 10T 1/2 cells transformed in vitro by x-rays or 3-methylcholanthrene.     

参麦注射液对高血压心衰大鼠血浆代谢组学的影响

目的 研究参麦注射液对高血压心衰大鼠血浆代谢组学的影响。方法 通过8% NaCl高盐饲料喂养Dahl盐敏感性大鼠制造高血压心衰模型,成模大鼠分为模型组、参麦注射液组,并同时设置正常组,干预15 d后,采集正常组、模型组和参麦注射液组大鼠的血浆样本,运用气相色谱-质谱（GC-MS）联用技术及多元统计分析进行研究。结果 3组的代谢图谱存在显著差异。与正常组相比,模型组19种代谢物水平紊乱;经参麦注射液干预后,亮氨酸、鸟氨酸、丙氨酸、4-羟基-脯氨酸、苏氨酸、天冬酰胺、苏糖醇、丙酮酸、尿素浓度向正常方向显著回调,苏糖酸、半胱氨酸、色氨酸、甲基半胱氨酸、花生四烯酸、胆固醇、木糖醇、核糖醇、焦谷氨酸、丙二酸浓度无显著改变,此外还发现异亮氨酸浓度上升。结论 高血压心衰大鼠血浆代谢组学出现变化,参麦注射液能有效改善部分紊乱的代谢物水平,其作用机制与改善糖代谢、氨基酸代谢紊乱,调节支链氨基酸水平相关,未发现有改善脂代谢紊乱的作用。     

Cytotoxic effect of lymphocyte-antigen interaction in delayed hypersensitivity

Lymph node cells from inbred rats having delayed sensitivity to soluble proteins inhibit growth of syngeneic or allogeneic fibroblasts in the presence of specific antigen. A relation is suggested between this in vitro phenomenon and other systems believed to be specific manifestations of delayed hypersensitivity.     

Transgenic mice with I-A on islet cells are normoglycemic but immunologically intolerant

Insulin-dependent diabetes mellitus (IDDM) is caused by a specific loss of the insulin-producing beta cells from pancreatic Langerhans islets. It has been proposed that aberrant expression of major histocompatibility complex (MHC) class II molecules on these cells could be a triggering factor for their autoimmune destruction. This proposal was tested in transgenic mice that express allogeneic or syngeneic class II molecules on the surface of islet cells at a level comparable with that normally found on resting B lymphocytes. These animals do not develop diabetes, nor is lymphocyte infiltration of the islets observed. This immunological inactivity does not result from tolerance to the "foreign" class II molecules.     

Mixed lymphocyte reaction: an in vitro test for antilymphocytic serum activity

When Lewis rats were exposed to antilymphocytic serum, produced in rabbits, to Lewis lymphoid cells, the transformation of their thoracic duct lymphocytes in response to foreign lymphoid cells was markedly reduced in comparison with that in response to similar cells from donors treated with saline or normal rabbit serum. It is suggested that the mixed lymphocyte reaction may be used as an in vitro test for the in vivo activity of antilymphocytic serum.     

Murine lymphoma-induced immunosuppression: requirement for direct tumour cell contact

The FBL-3 lymphoma cell line caused impaired antibody formation in vivo when injected into mice intraperitoneally, and in vitro when added to normal syngeneic spleen cells immunized in vitro with sheep erythrocytes. Immunosuppression occurred only when intact viable tumor cells were cocultivated with the normal spleen cells. As few as 10(5) FBL-3 cells, when added to 5 X 10(6) normal cells, impaired antibody formation. However, cell-free extracts of filtrates from even much larger numbers of tumor cells did not affect antibody formation, either in vitro or in vivo. Heating the tumor cells at 56 degrees C or irradiation with as little as 1000 rads completely abolished immunosuppressive activity, both in vitro and in vivo. Separation of viable tumor cells from target antibody-forming cells by cell-impermeable membranes prevented immunosuppression, showing that direct cell-to-cell contact is required for immunosuppression.     

1,25-dihydroxyvitamin D3 receptors in human leukocytes

A 1,25-dihydroxyvitamin D3 receptor macromolecule was detected in peripheral mononuclear leukocytes from normal humans. This macromolecule was found to be present in monocytes but absent from normal resting peripheral B and T lymphocytes. However, it was present in established lines of malignant B, T, and non-B, non-T human lymphocytes, as well as in T and B lymphocytes obtained from normal humans and activated in vitro.     

Rheumatoid factor secretion from human Leu-1+ B cells

A human B cell subpopulation identifiable by the expression of the cell surface antigen Leu-1 (CD5) is responsible for most of the immunoglobulin M rheumatoid factor secreted in vitro after the cells are stimulated with Staphylococcus aureus. The ability of B cells bearing the Leu-1 marker (Leu-1+) to secrete rheumatoid factor is present early in development and extends to adulthood, since Leu-1+ B cells from cord blood and from peripheral blood lymphocytes of both normal adults and patients with certain autoimmune conditions secrete rheumatoid factor in comparable amounts. The neonatal enrichment of Leu-1+ B cells, the presence of Leu-1+ B cells in increased frequencies in patients with autoimmune disease, and the involvement of Leu-1+ B cells in autoantibody secretion suggest both developmental and functional homologies between this human B cell subpopulation and the murine Ly-1 B cell subpopulation.     

Allergic encephalomyelitis: new form featuring polymorphonuclear leukocytes

The passive transfer of allergic encephalomyelitis can be produced in a single day. In work described, the procedure was made to coincide with a transient drug-induced deficiency of lymphocytes. As a result, the lesions of this autoimmune disease contained a predominance of polymorphonuclear leukocytes instead of the usual mononuclear cells. Not only is this a new histologic form of the disease, but the ready recognition of polymorphonuclears as reactive cells provides a powerful new tool for investigating the roles of immunologically specific effector cells and nonspecific reactive cells in production of tissue damage.     

Estrogenic induction of ornithine decarboxylase in vivo and in vitro

Injection of estrogens (17beta-estradiol or diethylstilbestrol) into immature chicks results in a marked (30- to 50-fold) increase in the ornithine decarboxylase activity of oviductal homogenates within a 4-hour period. Similar stimulations were obtained when estrogen was injected into hypophysectomized or castrated rats and the uterus was examined for decarboxylase activity. An elevation of decarboxylase activity was obtained in vitro when oviducts from immature chicks were incubated in the presence of estrogen. These data indicate a direct action of estrogen on oviduct tissue to promote a rapid increase in the activity of a specific enzyme and represent the first example of a completely in vitro enzyme response to estrogen.     

Mixed lymphocyte reactions and tissue transplantation tolerance

The induction of tolerance of Lewis histocompatibility antigens in BN rats inoculated at birth with BNI Lewis F(1) hybrid bone marrow cells, as revealed by the prolonged survival of Lewis skin grafts, is accompanied by markedly decreased reactivity in the mixed lymphocyte interaction. Blood lymphocytes from animals inoculated with lymph node cell suspensions also display diminished proliferative reactivity to hybrid BN/Lewis cells in the interaction. However, these recipients are not tolerant of Lewis skin grafts. Blood lymphocytes from BN rats inoculated neonatally with Lewis thymocytes fail to display any level of unresponsiveness in vitro, and such animals are not tolerant of Lewis skin grafts. The results suggest that in rats skin and marrow cells have histocompatibility antigens that are absent or poorly expressed on lymph node cells and thymocytes.     

Effect of lesions in the septal forebrain of the rat on sleeping time under barbiturate

Rats with electrolytic lesions in the septal forebrain show increased sleeping times after injection with thiopental sodium or barbital, as compared with normal and other control rats and rats with lesions in the cerebral cortex or caudate nucleus.