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W H Adler

Publications and source records attributed to W H Adler.

At least 91 records · Page 5Linked to original sources
PubMed1982

Cyclosporin a inhibits T cell-mediated augmentation of mouse natural killer activity.

Cyclosporin A (CSA) in vitro inhibited the spontaneous cytotoxic activity of mouse spleen cells against YAC target cells in a 4 hr 51Cr release assay. While natural killer (NK) cells were inhibited directly by CSA, these suppressive effects were largely reversible by coculture of effector cells for an optimal period with polyinosinic-polycytidylic acid (Poly I:C) or lipopolysaccharide (LPS). In contrast concanavalin A (Con A), in the presence of CSA, was unable to augment NK activity. The supernatant, however, of mouse spleen cells cultured with Con A was fully able to augment the NK the activity by freshly cultured spleen cells in the presence of CSA. The results indicate that CSA inhibits NK activity by two distinct mechanisms: a) a direct inactivation of NK cells and b) a suppression of production or release of an NK-activating factor from T cells, but not B cells or macrophages.

Animals↗
PubMed1982

Oxidative metabolism and bactericidal capacity of polymorphonuclear leukocytes from normal young and aged adults.

The ability of polymorphonuclear leukocytes (PMNs) from young and old individuals to reduce nitroblue tetrazolium, to kill Staphylococcus aureus in vitro, and to generate superoxide was determined. Investigation of PMNs from 202 humans, aged 26 to 95 years, failed to demonstrate an age relationship in their ability to reduce nitroblue tetrazolium. The ability of PMNs from 20 young (M age 34 years) individuals to kill S. aureus in vitro did not differ from cells from 18 elderly (M age 68 years) persons. Mean production of superoxide in response to stimulation with latex particles was, however, significantly lower (P less than .001) in cells from elderly adults. These results suggest a heterogeneity in any age-associated defect in PMN function. Several aspects of PMN function need to be evaluated in order to describe overall PMN function in the elderly.

Adult↗
PubMed1982

Inhibition of mouse natural killer activity by cyclosporin A.

Cyclosporin A(CSA), administered in vivo or in vitro, inhibited the spontaneous cytotoxicity of C57BL/6 and NZB/WF1 mouse spleen cells against YAC and K562 target cells in a 4 hr 51Cr release assay. Inhibition of natural killing (NK) by CSA occurred rapidly, was dose-dependent, and did not require the presence of T cells, B cells or macrophages. CSA depressed NK activity by direct interaction with NK cells. There was no evidence that inhibition of NK by CSA was mediated through suppressor cells.

Animals↗
PubMed1982

Regulation of natural killer activity in vivo. III. Effect of hypophysectomy and growth hormone treatment on the natural killer activity of the mouse spleen cell population.

Spleen natural killer (NK) activity against YAC tumor cells was reduced in female C57BL/6J mice hypophysectomized at 3 weeks and sacrificed 4-8 weeks later. Proportions of null cells and of target binding cells in spleens from hypophysectomized and sham operated mice were significantly different. Administration of ovine growth hormone (GH) (100 microgram/day, i.p. for 10 days) resulted in a marked recovery of NK activity in hypophysectomized mice. NK activity by spleen cells from hypophysectomized or sham operated mice (with or without GH treatment) was mediated by non-T, non-B lymphocytes.

Animals↗
PubMed1982

Identity of effector cells participating in the reverse antibody-dependent cell-mediated cytotoxicity.

Our previous work has shown that antibody-coated mouse spleen cells express enhanced cytotoxic activity against some Fc-receptor-bearing target tumour cells by a mechanism which appears to be similar to an antibody-dependent cell-mediated cytotoxicity (ADCC) reaction with reversed polarity of the antibody bridge (R-ADCC). In this report we have shown that (i) the levels of basal natural killer (NK), ADCC and R-ADCC cytotoxic activities in mouse spleen cells are strongly correlated with each other, (b) simultaneous induction of ADCC and R-ADCC reactions does not result in an additive cytotoxic response, and (iii) YAC cells which do not bear Fc receptors and are highly sensitive to lysis by NK cells, can specifically and competitively inhibit the ADCC and R-ADCC reactions. These results suggest that the R-ADCC reaction may be mediated by the same effector cell population as mediates NK and ADCC reactions against tumour target cells.

Animals↗
PubMed1982

Mitogenic activity of 12-O-tetradecanoyl phorbol-13-acetate on peripheral blood lymphocytes from young and aged adults.

The effect of age on the proliferative response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) was examined using peripheral blood lymphocytes from 185 adults. TPA-induced DNA synthesis measured by cellular 3H-thymidine incorporation was found, like the responses of cells activated by PHA and Con A, to markedly diminish with advancing age. The presence of indomethacin (1 microgram/ml) or Ro 20-5720 (10 micrograms/ml) in TPA activated cell cultures, unlike PHA stimulated cultures, did not result in augmentation of 3H-thymidine incorporation by cells from elderly individuals. These results demonstrate that prostaglandin synthesizing suppressor cells are not responsible for the age-related depression of cellular immune function observed in TPA activated cells and confirm the observation that decreased production and/or utilization of soluble mediators, such as IL-2, may account for the diminished mitogen responsiveness of lymphocytes from elderly individuals.

Adult↗
PubMed1981

Enumeration of T lymphocyte subsets by monoclonal antibodies in young and aged humans.

The percentage and absolute number of peripheral blood mononuclear cells reactive with monoclonal antibodies identifying mature thymocytes and T cells (T3+), helper/inducer cells (T4+), and suppressor/cytotoxic cells (T8+) was determined in 19 young (mean age 35 yr) and 31 elderly (mean age 72 yr) individuals. The percent representation but not the absolute number of T cells (T3+) declined significantly (p less than 0.001) in the elderly, and the decline was attributable to both an absolute and relative decrease in the representation of the subpopulation of cytotoxic/suppressor (T8+) cells. The percentage and number of helper/inducer (T4+) T cells was comparable in both age groups.

Adult↗
PubMed1981

Spontaneous or natural killer cytotoxicity of K562 erythroleukemic cells in normal patients.

Peripheral blood mononuclear cells from 200 normal individuals, ages 20 to 95 years, were evaluated for their capability to mediate spontaneous or natural killer (NK) cytotoxicity using the K562 erythroleukemic cells as targets. The results of a 4-hr 51Cr specific release assay demonstrated that the NK activity of normal individuals is independent of age, sex, and smoking habits. Although varying greatly among individuals, the NK activity of 25 persons restudied after a mean 20-month interval remained stable. Deficient NK lytic activity is not characteristic of elderly individuals.

Adult↗
PubMed1981

Human B cell function in normal individuals of various ages. 1. In vitro enumeration of pokeweed-induced peripheral blood lymphocyte immunoglobulin-synthesizing cells and the comparison of the results with numbers of peripheral B and T cells, mitogen responses, and levels of serum immunoglobulins.

The effect of age on the in vitro generation of immunoglobulin-secreting cells in pokeweed mitogen-stimulated cultures was examined using a staphylococcal protein A plaque assay. Although there was no statistically significant decrease with age in the numbers of plaque-forming cells, subjects whose cells failed to produce immunoglobulin were four times more common amongst individuals over 55 years of age. Simultaneously-measured T and B lymphocyte numbers. 3H-thymidine incorporation by mitogen-stimulated cultures, and serum immunoglobulins were comparable in both the young and the aged.

Adult↗
PubMed1980

Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity.

Natural killer (NK) activity of human peripheral blood lymphocytes (HPBL) was studied in 32 alcoholics and 15 control subjects in a 4-h chromium release assay using K562 tumor target cells. The natural killer activity of human peripheral blood lymphocytes in alcoholics was significantly higher than the level found in the control group. NK activity of PBL from alcoholics was still higher than that of similarly treated PBL from control subjects after carbonyl iron and magnet treatment, or after passage through a nylon wool column or after removal of cells rosetting with sheep erythrocytes. Changes in T cell, B cell or macrophage populations, therefore, are not the mechanism for increased NK activity in alcoholics.

Adult↗
PubMed1980

Monoclonal anti thy 1.2 antibodies from hybridoma HO13-4 do not react with mouse natural killer cells.

The susceptibility of NK cells and immune cytotoxic T-cells to treatment with (a) monoclonal anti thy 1.2 antibodies from hybridoma HO13-4, (b) rabbit anti-mouse T-cell antiserum and (c) gamma globulins prepared from AKR/J anti C3H/HeJ antiserum was studied in the presence of rabbit complement. Monoclonal anti thy 1.2 antibody treatment completely abolished the cytotoxic activity of immune T-cells derived from C57BL/6J mice (H-2b) immunized with (C57BL/6J x DBA/2)F1 spleen cells (H-2bd) against P815 (H-2d) target cells. The same treatment had no significant effect on the NK activity of spleen cells from unimmunized mice against YAC target cells. Rabbit anti-mouse T-cell and mouse anti theta antisera also abrogated completely the immune T cell activity of spleen cells. This treatment however also resulted in a partial loss of NK activity. These results indicate that conventional anti theta antisera contain antibodies which recognize antigenic specificities on T-cells as well as on a population of NK cells. The cross reactivity is not a result of thy 1.2 antigen expression on NK cells and T-cells as recognized by the monoclonal antibodies. The specificity recognized by the monoclonal antibody (HO13-4) is only expressed on T-cells.

Animals↗