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J C Roder

Publications and source records attributed to J C Roder.

At least 145 records · Page 8Linked to original sources
PubMed1979

Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides.

Dibutyryl cAMP (dB-cAMP) and the cAMP elevating agents, prostaglandin E1, theophylline, and histamine markedly suppressed NK cytolytic function in a dose- and rate-dependent manner. The inhibition was rapidly induced and persisted in the presence of the drugs. Separate pretreatment of targets and highly purified NK cells, isolated by a target binding and velocity sedimentation technique, revealed that PGE1 and dB-cAMP acted at the level of the effector cell in a short-term cytolytic assay. In contrast to the inhibitory effects of cAMP elevating agents, dB-cGMP and carbamylcholine caused a small but significant acceleration in the rate of lysis and could compete with inhibitory doses of dB-cAMP to reduce the level of suppression thereby suggesting that the cAMP-cGMP ratio might be important in NK-mediated lysis. Insulin had no effect on NK activity, whereas T cell-mediated cytolysis was augmented by insulin and cGMP if the effector cells were taken early after alloimmunization but not later. Neither cAMP- nor cGMP-elevating agents affected the frequency of NK-target cell conjugates. These results are compatible with the hypothesis that cyclic nucleotides may be involved in triggering the lytic event within NK cells.

Animals↗
PubMed1979

Immunological senescence. II. Normal in vitro colony formation by B cells from old mice.

The in vitro frequency and proliferative capacity of B cells and B-cell precursors in old mice was assessed. The mitogenic response to the B-cell mitogens lipopolysaccharide (LPS) and dextran sulphate decline later and at a slower rate than the T-cell response to phytohaemagglutinin and concanavalin A. The response to precursor B-cell mitogen dextran sulphate was not depressed in the bone marrow of aging mice. In addition, the dose response and kinetics of LPS and mercaptoethanol stimulated B-cell colony formation in agar was identical in spleen cells from young and old mice. These results indicate that the intrinsic proliferative capacity of B cells from old mice is normal.

Aging↗
PubMed1979

The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function.

A point mutation, called beige, on linkage group 14 in C57BL/6 mice leads to a marked impairment in natural killing and antibody-dependent, cell-mediated cytolysis (ADCC) of tumor cells. The defect in NK cytolysis was predetermined at the level of progenitor cells in the bone marrow as revealed in radiation chimeras. This impairment in NK function could not be accounted for by an altered organ distrubution, target selectivity, or ontogenesis. Interferon did not fully restore the response, which suggests that the defect may not result solely from a lack of endogenous interferon stimulation in beige mice. The frequency of target-binding cells was normal in all lymphoid organs, which suggests that the defect is intrinsic to the NK cell and does not involve an altered population size or an inability to recognize and interact with the target. Rather, the defect may lie within the lytic pathway subsequent to target cell contact. These mice should provide a useful NK-deficient system for studies of T cell or macrophage immunity and in addition they provide a means for testing the in vivo significance of NK cells in resistance to tumors and virus-infected cells.

Animals↗
PubMed1978

Loss of self-tolerance to single-stranded deoxyribonucleic acid (sDNA) in vitro.

The spleens of many normal and autoimmune-susceptible strains of mice mount a specific, IgM, anti-sDNA plaque-forming cell (PFC) response in vitro in the absence of an exogenous source of antigen. This response was not related solely to levels of xenotropic or ecotropic virus and was generated from a small number of precursor cells capable of binding sDNA. Small numbers of anti-sDNA PFC were also apparent in serum-free medium and the response of low-responder strains could be augmented with pokeweed mitogen. T cells and macrophages were not essential and cell division was required early in culture to obtain a peak response on day 5. These results suggest that autoantigen-sensitive cells may escape normal regulatory mechanisms in vitro and differentiate into clones of autoantibody secreting cells.

Animals↗
PubMed1978

Regulation of the autoimmune plaque-forming cell response to single-strand DNA (sDNA) in vitro.

We have shown that young autoimmune and normal strain mice possess autoantigen-sensitive cells potentially capable of producing anti-sDNA autoantibody in the absence of normal regulatory mechanisms in vitro. In certain strains such as B/W mice, these regulatory mechanisms presumably break down with increasing age, and autoimmunity develops. These regulatory mechanisms might consist of sDNA, T cells, or some combination of these since both of these agents suppressed the anti-sDNA PFC response in vitro. The sDNA may have inhibited PFC development by a receptor blockade mechanism since i) spleen cells pulsed with sDNA for short periods and then washed were suppressed after 5 days of culture; ii) treatment of these blocked cells with trypsin and DNase I restored the anti-sDNA response; iii) the PFC remaining in partially blocked cultures were of lower avidity than PFC in unblocked cultures; and iv) the target of sDNA may be a B cell. Thymocytes and splenic T cells suppressed the anti-sDNA response but not the anti-SRBC response in vitro in a dose-dependent manner. The suppressive capacity of thymus cells did not decline with age in B/W mice. In addition, thymus cells activated by competing foreign antigens could also suppress the anti-sDNA response. The relationship between these modes of regulating autoreactivity remains to be investigated.

Animals↗
PubMed1978

Regulation of the immune response in autoimmune NZB/NZW F1 mice. II. Age dependent release of suppressive factors from spleen cells.

Supressor cells in the spleens of overtly autoimmune NZB X NZW (B/W) mice, but not age matched normal strain mice, were shown to release a small, less than 20,000 Dalton factor which inhibited early events in the anti-SRBC PFC response and the mitogenic response. This splenic inhibitory factor (SIF) was (i) stable on heating (56 degrees, 30 min) and freezine (-70degrees); (ii) non-specific for antigen; (iii) absorbed and/or inactivated by target cells in young B/W spleen cell cultures and (iv) released gradually into the culture medium by metabolically active cells. SIF also blocked the T-cell replacing effect of allogeneic factor (TRF) in the anti-SRBC response. These observations suggest that SIF may lead to the immunodepressed state in overtly autoimmune B/W mice by preventing the activation or differentiation of lymphocytes responding to exogenous antigen.

Aging↗
PubMed1978

Immunological senescence. I. The role of suppressor cells.

The in vitro anti-SRBC response of several murine strains declined markedly with age in parallel with an increase in the activity of suppressor cells in the spleen and bone marrow which prevented early events during the induction of the immune response. These suppressor cells released soluble mediators and lacked the characteristics of mature T cells or macrophages. In addition the suppressor cell in the bone marrow could be removed on anti-Ig columns and fractions of old splenic suppressor cells sedimenting at 0.32 cm/h were greatly enriched in surface Ig bearing cells. Old immunodepressed mice did not lack potentially immunocompetent cells since the antibody response of old spleen cells could be restored by specifically activated T cells or lipopolysaccharide which act on B cells. These results suggest that a rise in the activity of non-T suppressor cells in the spleen and bone marrow may account, in part, for the depression in humoral immunity observed in aging mice.

Aging↗
PubMed1976

Cell interaction in B/W mice: a reversible defect at the T-cell level.

The anti-SRBC PFC response of old B/W mice can be restored by adding specifically activated T cells or primed spleen cells in vitro as well as by injecting LPS and SRBC in vivo. Since nonresponsive old B/W bone marrow and thymocytes cooperated in a normal manner upon adoptive transfer, this suggested that the lack of response to SRBC in the intact animal was due to a block in T cell activation and not due to intrinsic defects in lymphoid cells necessary to initiate a response. The block in T cell activation might be mediated by a suppressor cell found in old B/W spleens and it was hypothesized that this suppressor might also lead to a loss of self-tolerance.

Aging↗
PubMed1975

T cell activation and cellular cooperation in autoimmune NZB/NZW F hybrid mice.

Old (6 months) overtly autoimmune female NZB X NZW F1 (B/W) mice were markedly hyporesponsive to sheep erythrocytes (SRBC). The response to SRBC was restored by a) simultaneously injecting lipopolysaccharide (LPS) with SRBC or b) transferring bone marrow and thymocytes with SRBC into lethally x-irradiated (100 R) syngeneic old recipients. The in vitro PFC response of old B/W spleen cells to SRBC was restored by adding in culture a) theta-positive and radioresistant spleen cells from old B/W mice primed with homologous antigen or b) activated T cells from the spleens of lethally x-irradiated (1000 R) old B/W mice injected with old syngeneic thymocytes and SRBC but not horse erythrocytes. Various populations of unprimed lymphoid cells from young (4 to 6 weeks) female B/W mice, which respond normally to SRBC, were not capable of restoring the response of old syngeneic mice in vitro or in vivo. These results suggest the existence of a suppressor of T cell activation and/or B and T cell interaction in old autoimmune B/W mice.

Absorption↗
PubMedDate not supplied

NK-mediated reduction of malignancy in human melanoma cells treated with theophylline.

Theophylline-treated cells of the human melanoma line showed an increase in NK-sensitivity in vitro and a concomitant decrease in tumorigenicity and spontaneous metastasis in Balb/c nude mice. The MeWo cells were heterogeneous and contained related subpopulations which were cloned to produce two cell lines, one hypodiploid (Cd-16) and one hypotetraploid (Ct-1). Prolonged (3 months) or short-term (4 days) treatment of these cell lines with 1 mM theophylline markedly reduced the incidence and size of tumors in Balb/c nude mice early after s.c. injection and their ability to metastasize spontaneously to the lung was also reduced. The effect was much more pronounced with Cd-16 cells, which contain amplified DNA compared to Ct-1 cells which lack DNA amplification. Part of the tumor inhibition caused by theophylline was due to natural killer (NK) cells. Thus, in vivo treatment of nude mice with anti-asialo GM1, a procedure known to remove NK cells, partially reversed the inhibitory effects of theophylline on tumor formation and generation of metastasis by Cd-16 cells. Consistent with this observation theophylline treatment enhanced the in vitro NK sensitivity of Cd-16 cells four-fold whereas Ct-1 was enhanced only slightly. The data suggest that theophylline can act preferentially on certain tumor cell subpopulations to enhance their NK-sensitive phenotype and thereby inhibit their capacity to form tumors and to metastasize in nude mice.

Animals↗
PubMedDate not supplied

The in vivo clearance of Ha-ras transformants by natural killer cells.

The experiments in this study were designed to test the hypothesis that natural killer (NK) cells play a role in host surveillance against early neoplastic changes in the malignant process. C3H 10T1/2 mouse fibroblasts were transfected with a pSV2-neo plasmid vector which contains EJ, the mutated c-Ha-ras, regulated by its own promoter. Control cells were transfected with pSV2-neo alone and did not contain the ras gene. Oncogene-transfected cells were compared with control cells for lung colony formation following tail vein injection into C3H mice. Intravenous injection of ras-transfected 10T1/2 cells induced marked lung colony formation in vivo, whereas C3H 10T1/2 parental lines or 10T1/2 cells transfected with pSV2-neo alone induced no lung colonies in C3H mice. The colonising potential of ras transfectants could be decreased by augmentation of NK activity by injection of polyinosinic cytidylic acid and increased by depletion of NK effectors with anti-asialo GM1. Experiments with beige mice demonstrated that the mortality of syngeneic, NK-deficient C3H-bg/bg mice injected with ras tranfectants was significantly greater than similarly treated NK-normal C3H(-)+/bg littermate controls. The results support the view that NK cells are capable in vivo of recognizing early defined stages in the neoplastic process initiated by oncogenes.

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