Function Of Lymphoid Cells Research Articles

A Diffusible Stimulator of Eosinophilopoiesis Produced by Lymphoid Cells as Demonstrated With Diffusion Chambers

Previous experiments have indicated that eosinophilopoiesis is stimulated in lymphoid cell-dependent eosinophil responses to certain antigens. In order to study if the potential for this stimulation of eosinophilopoiesis is a function of lymphoid cells and can be expressed on challenge with the eosinophilia-inducing antigen, the diffusion chamber technique for the culture in vivo of murine hemopoietic cells has been modified. A quadrachamber diffusion assembly allows for the simultaneous maintenance in the same host of four cell populations, pairs of which are separated by a cell-impermeable Millipore diffusion membrane of defined porosity. Spleen cells for chambers were from normal mice and mice primed with tetanus toxoid; secondary challenge induces eosinophilia. These spleen cells were placed transfilter from isogeneic bone marrow cells and cultured in vivo for 6 days in normal mice that received tetanus toxoidintraperitoneally following chamber-assembly implant. The marrow cell transfilter from spleen cells of primed-donor origin exhibited significantly greater eosinophilopoiesis than contiguous-chamber marrow transfilter from normal spleen cells. Such stimulated eosinophilopoiesis was independent of total chamber marrow cellularity. The data indicated that antigen-stimulated lymphoid cells may be the source of an eosinophilopoietic factor.

A diffusible stimulator of eosinophilopoiesis produced by lymphoid cells as demonstrated with diffusion chambers

Previous experiments have indicated that eosinophilopoiesis is stimulated in lymphoid cell-dependent eosinophil responses to certain antigens. In order to study if the potential for this stimulation of eosinophilopoiesis is a function of lymphoid cells and can be expressed on challenge with the eosinophilia-inducing antigen, the diffusion chamber technique for the culture in vivo of murine hemopoietic cells has been modified. A quadrachamber diffusion assembly allows for the simultaneous maintenance in the same host of four cell populations, pairs of which are separated by a cell-impermeable Millipore diffusion membrane of defined porosity. Spleen cells for chambers were from normal mice and mice primed with tetanus toxoid; secondary challenge induces eosinophilia. These spleen cells were placed transfilter from isogeneic bone marrow cells and cultured in vivo for 6 days in normal mice that received tetanus toxoidintraperitoneally following chamber- assembly implant. The marrow cell transfilter from spleen cells of primed-donor origin exhibited significantly greater eosinophilopoiesis than contiguous-chamber marrow transfilter from normal spleen cells. Such stimulated eosinophilopoiesis was independent of total chamber marrow cellularity. The data indicated that antigen-stimulated lymphoid cells may be the source of an eosinophilopoietic factor.

Lymphocyte Populations and Cellular Immune Reactions in Juvenile Rheumatoid Arthritis

Ten patients with juvenile rheumatoid arthritis and age‐ and sex‐matched healthy controls were investigated in pairs. The patients were found to have both normal proportions and normal absolute numbers of T lymphocytes, B lymphocytes, and the Fc‐receptor‐bearing lymphoid cells in peripheral blood. No abnormality of mitogen‐induced lymphocyte transformation was observed. Lymphocyte‐mediated cytotoxicity induced by phytohemagglutinin (PHA) or anti‐target cell antibodies was also found to be normal. As in an earlier study, impaired delayed hyper‐sensitivity by skin testing was observed in the patient group, thus indicating a dissociation between in vivo and in vitro parameters of lymphoid cell function.

Lymphocyte Populations and Cellular Immune Reactions in Juvenile Rheumatoid Arthritis

Ten patients with juvenile rheumatoid arthritis and age- and sex-matched healthy controls were investigated in pairs. The patients were found to have both normal proportions and normal absolute numbers of T lymphocytes, B lymphocytes, and the Fc-receptor-bearing lymphoid cells in peripheral blood. No abnormality of mitogen-induced lymphocyte transformation was observed. Lymphocyte-mediated cytotoxicity induced by phytohemagglutinin (PHA) or anti-target cell antibodies was also found to be normal. As in an earlier study, impaired delayed hypersensitivity by skin testing was observed in the patient group, thus indicating a dissociation between in vivo and in vitro parameters of lymphoid cell function.

Lysosomal and mitochondrial enzyme activities in human lymphoid cell lines obtained from children with acute lymphoblastic leukemia and controls

The activities of seven lysosomal and three mitochondrial enzymes from isolated lysosomes and mitochondria of cultivated lymphoid cell lines, obtained from 3 patients with leukemia and from 6 normal individuals, were investigated. The lysosomal enzymes included: α-glucosidase, β-glucosidase, β-galactosidase, β-glucuronidase, N-acetyl-β-glucosaminidase, aryl sulfatase and acid phosphatase. These enzymes are involved in the degradation of glycoprotein, glycolipids, mucopolysaccharide-protein complexes, polysaccharides, mucopolysaccharides, organic sulfates and phosphoric esters. In the mitochondrial fraction, glutamic, succinic and malic dehydrogenases were studied. The range of lysosomal enzyme activities obtained from cell lines of leukemic origin was found to be consistently higher than in the normal controls [200 % (aryl sulfatase) to 732% (β-glucosidase)]. The mitochondrial enzyme activities showed only slight differences between the leukemic and control cell lines. This study demonstrates that the lysosomal functions of lymphoid cells derived from patients with acute lymphoblastic leukemia are fundamentally different from those from healthy donors.

Cellular structure and function in normal and neoplastic lymphoid cells

In general, the ultrastructure of normal lymphocytes and plasma cells reflects their functional state. Similarly, in pathologic conditions, ultrastructural abnormalities may reflect specific functional derangements of the cells. The identification of some structural abnormalities may be clinically useful, even though their origin and biochemical composition is still obscure.

The endocrine role of the thymus and its hormone, thymosin, in the regulation of the growth and maturation of host immunological competence.

This chapter describes the endocrine role of the thymus and its hormone, thymosin, in the regulation of the growth and maturation of host immunological competence. The essential role of thymosin, and perhaps of other thymic factors, in growth and development is reflected in the two established roles of the thymus gland. These are: (1) the provision in early postnatal life of lymphoid cells that are exported from the thymus to the peripheral lymphoid structures and which become a cell population that endows the neonatal organism with immunological competence, and (2) the secretion from thymic epithelial cells of one or more hormones, one of which is thymosin. These humoral factors apparently function by acting on both stem cells and thymus-derived cells to activate and/or depress a cell that has all the potential to function as a mature immunologically competent lymphocyte. In addition, thymosin may act to reverse aberrations of lymphoid cell functions, for example, proliferation of aberrant thymocytes.

Selective defects of in vitro parameters of lymphoid cell function in patients with irradiated testicular tumour and in patients with lymphoproliferative disorders.

The capacity of lymphoid cells to manifest in vitro cytotoxicity against chromium‐labelled chicken erythrocytes in the presence of PHA or antibodies to chicken erythrocytes was studied in 24 patients with testicular tumours who had received extended abdominal field irradiation, and in five patients with malignant lymphomas. The PHA‐induced cytotoxicity in patients with irradiated testicular tumour was significantly lower than that in the normal controls, while no significant difference in antibody‐induced cytotoxicity was found. In four of the patients, a markedly impaired cytotoxic response to PHA was found in spite of normal DNA synthesis induced by this mitogen. Two patients failed to respond to PHA both by cytotoxicity and DNA synthesis. A deficient PHA‐induced cytotoxicity, but normal cytotoxic activity in the presence of anti‐target cell antibodies, was observed in six of the patients. These dissociations in terms of in vitro parameters of lymphocyte function may reflect selective depression of lymphocyte subpopulations resulting from radiotherapy or disease processes.

Thymus-dependent and thymus-independent effector functions of mouse lymphoid cells. Comparison of cytotoxicity and primary antibody formation in vitro

We have compared two effector functions, antibody formation and cytotoxic capacity in vitro, of mouse cells of various origin with special reference to the T lymphocyte dependence of these processes. We have used addition of PHA and coating of target chicken erythrocytes (CRBC) with antibody as the two means of inducing cytotoxicity. Antibody formation in vitro has been studied both against thymus-dependent sheep erythrocytes (SRBC) and thymus-independent ( E. coli) antigens. Spleen cells from thymectomized, lethally irradiated bone marrow-, or fetal liver-repopulated mice were deprived of phagocytic cells by uptake of colloidal iron. They did perform better than normal spleen cells in the antibody-induced cytotoxicity and were also induced to cytotoxicity by PHA. PHA did not induce increased DNA synthesis in these T cell-deprived spleen cell preparations, which could not make primary antibodies to SRBC but were able to do so against E. coli antigens. Fresh bone marrow and fetal liver cells, deprived of phagocytic cells, were also induced into a highly efficient cytotoxicity by anti-CRBC as well as by PHA. Pretreatment of spleen cells with an alloantiserum (θ) against T lymphocytes reduced but did not abolish the PHA-induced cytotoxicity. In contrast, it did not affect the antibody-induced cytotoxicity. Such treated cells could not make antibodies to SRBC but could do so against E. coli. Pretreatment of spleen cells with a heteroantiserum (MBLA) against mouse B lymphocytes completely abolished all cytotoxic- and antibody-forming abilities of the cells, although experiments with combinations of θ-treated and MBLA-treated cells suggested that the MBLA treatment had left behind a significant portion of helper T cells needed for the in vitro antibody response. From these data we conclude, as have others, that the antibody-induced cytotoxicity is independent of T lymphocytes. It can be induced in immature precursor cells from fetal liver or bone marrow, and these cells may also become cytotoxic on interaction with PHA. However, in normal spleen cells, at least part of the PHA-induced cytotoxicity is T cell dependent. Some preliminary data suggest that this PHA-induced cytotoxicity of normal spleen cells may be a joint process between T lymphocytes and other cells.

Lymphocyte monovalent cation metabolism: Cell volume, cation content and cation transport

AbstractMechanisms which determine sodium and potassium content and volume of rat thymic and human chronic lymphocytic leukemia (CLL) lymphocytes have been studied. The deleterious effect of cell isolation on monovalent cation content was proven by comparing thymus sodium and potassium concentration to that of thymocytes prepared from autologous hemithymus. In vivo distribution ratios of sodium‐24 and potassium‐42 between thymus water and plasma water were very similar to the distribution ratios of non‐radioactive isotopes (sodium‐23 and potassium‐39). The similar lymphocyte: thymocyte ratio of (a) cell volume (1.48), (b) cell sodium plus potassium (1.47) and (c) cell water (1.50) demonstrated the close correlation of lymphocyte volume with monovalent cation content and water content. Steady‐state CLL lymphocyte sodium (32 ± 1.9 mM) and potassium (131 ± 5.1 mM) and thymocyte sodium (31 ± 1.2 mM) and potassium (136 ± 3.9 mM) were similar; however, these steady‐state levels were maintained by quantitatively different membrane functions. Radiopotassium and radiosodium uptake by thymocytes was more rapid than by CLL lymphocytes. Ouabain‐sensitive potassium influx was 2.4 times greater in thymic (8.70 ± 2.28 mmoles/cm2/min × 10−8) than in CLL (3.24 ± 0.45 mmoles/cm2/min × 10−8) lymphocytes. Potassium exodus was also slower in CLL lymphocytes as compared to thymocytes. Ouabain‐sensitive sodium accumulation and ouabain‐insensitive sodium accumulation were also slower in CLL lymphocytes than in rat thymocytes. Half‐maximal ouabain inhibition of sodium entry was 7.5 × 10−3 M in thymic and CLL lymphocytes. The inhibitory effect of ouabain on sodium and potassium transport was easily reversible. Oligomycin inhibited ouabain‐sensitive potassium accumulation in both lymphocyte types. Four lines of evidence indicate the presence in the lymphocyte of a system of leaks and pumps, the latter subserved by a ouabain and oligomycin‐sensitive (sodium‐potassium) ATPase: (a) steady‐state monovalent cation gradient (K ∼ 20:1, Na ∼ 5:1), (b) the inability to maintain normal sodium and potassium gradients at cold temperature and in the presence of ouabain, (c) the effect of ouabain and oligomycin on active potassium influx and (d) the restitution of steady‐state sodium and potassium concentration after cell isolation, ouabain treatment and cold exposure. CLL lymphocytes as compared to rat thymocytes have a decreased rate of ouabain‐insensitive sodium uptake and potassium exodus requiring a reduced rate of active sodium extrusion and potassium accumulation to maintain steady‐state cation content. Ouabain‐sensitive ATPase is difficult to locate in lymphocytes in vitro possibly because it comprises a very small proportion of membrane ATPase since magnesium activated ecto‐ATPase in intact lymphocytes is 1500 to 2500 times that of the intact erythrocyte. The inhibition by ouabain of blast transformation, mitosis, amino acid accumulation and nucleic acid synthesis in vitro, may reflect the importance of ouabain‐sensitive ATPase and monovalent cation transport in the function of lymphoid cells.

Anti-DNA Plaque-Forming Cells (PFC) and Rosette-Forming Cells (RFC) in Spleens of NZB/W F1 Female (B/W) Mice

Abstract NZB female × NZW male F1 hybrid (B/W) mice spontaneously develop an autoimmune disease similar to human systemic lupus erythematosus (SLE)4 characterized by the appearance of antinuclear antibodies and fatal glomerulonephritis (1). Although a variety of autoantigens may be involved, anti-DNA has been strongly implicated in the pathogenesis of the renal disease (2, 3). The detectable anti-DNA in the serum is directed predominantly to determinants on single stranded DNA (4, 5). One of the critical questions with respect to autoimmune diseases in general is whether lymphoid cell function is normal, or if in fact there is altered function of thymic dependent (T) or thymic independent (B) lymphocytes. Although other investigators have approached this problem by examining the cellular response to heterologous antigens in the B/W mouse, similar approaches to autoantigens have not been reported. The present study describes preliminary experiments which demonstrate that the spontaneously occurring immune response to single stranded deoxyribonucleic acid (S-DNA) in B/W mice can be readily detected and quantitated by the hemolytic plaque assay.

L-asparaginase-induced immunosuppression: effects on antibody-forming cells and serum titers.

Treatment of mice with L-asparaginase from Escherichia coli resulted in a marked suppression of the immune response, as assessed both cellularly and humorally. Suppression occurred only when the enzyme was injected together with the sheep erythrocytes used as antigen. There was little or no effect when the enzyme was injected before the antigen. Simultaneous injection of asparagine prevented suppression, an indication that the effect of the enzyme was due to depletion of an amino acid probably essential for normal lymphoid cell function during antibody production.

In Vitro Effects of Phytohemagglutinin and Brain Antigen on Cell Transfer of Experimental Autoimmune Encephalomyelitis in Lewis Rats

Summary In order to study further the role of lymphoid cells in experimental autoimmune encephalomyelitis (EAE), lymph node cells from Lewis rats sensitized to nervous tissue-adjuvant were cultured under different conditions in vitro before their injection into recipient rats. Transfer of EAE was obtained consistently using 200 or 300 × 106 or more lymph node cells not cultured but directly injected into recipients. Culture of lymph node cells for 1 to 4 hr at 37°C diminished transfer capacity, more cells being required to obtain transfer results comparable to those with noncultured cells. Transfer activity of lymph node cells was not augmented by incubation with phytohemagglutinin. Incubation with brain antigen also did not increase activity but actually resulted in a marked decrease in transfer competence. These results are discussed in terms of mechanisms of EAE and immunologic functions of lymphoid cells.

Inhibitory Effect of Carcinostatic Agents on Antitumour Activity of Immune Lymphoid Cells

IT has been widely demonstrated that in vivo application of carcinostatic agents inhibits the host immune response, namely, inhibition of antibody production by antimetabolites1–4, alkylating agents1,5 and antibiotics6,7, and prolongation of homograft survival by a nitrogen mustard derivative8. Investigations of the mode of action of these agents on the immune function of lymphoid cells sensitized with homologous cells would provide interesting information on the mechanism of action of the lymphoid cells in transplantation immunity, since some of these agents have been known to act on the specific sites of the cellular functions.