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A Kinarty

Publications and source records attributed to A Kinarty.

31 records · Page 2Linked to original sources
PubMed1991

Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity.

We studied B cells from 18 patients with B-CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL-6. Our aim was to determine whether the increased incidence of autoimmune disease found in B-CLL patients is associated with enhanced spontaneous IL-6 secretion. IL-6 was measured by the effect of B cell supernatants on the proliferation of an IL-6 dependent plasmacytoma cell line T1165. The highest IL-6 values (7.4 +/- 1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B-CLL and concomitant autoimmune disease. The maximal IL-6 values for 10 patients with B-CLL only were 2.8 +/- 0.3 U/ml and for 10 age-matched controls, 0.8 +/- 0.3 U/ml (P less than 0.01, each group compared with the other). We conclude that there is an association between B-CLL, autoimmune disease and the spontaneous in vitro secretion of IL-6. Further studies are needed to determine whether the IL-6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B-CLL.

Aged↗
PubMed1990

Concomitant effect of 2'-deoxycoformycin on natural killer cell activity and tumour cell sensitivity to lysis in hairy cell leukaemia--discordant effects of alpha interferon.

The effects of 2'-deoxycoformycin (dCF) and alpha interferon (IFN-alpha) on natural killer (NK) cell-enriched fractions and hairy cell (HC) targets from three patients with HC leukaemia (HCL) were investigated. There was no significant increase in NK activity when either the HC targets or NK-enriched cells were preincubated with dCF. However, preincubation of both HC and NK cells with dCF resulted in increased NK activity. Culture of enriched NK cells with IFN-alpha enhanced their activity. However, preincubation of HC targets with this drug in the presence or absence of dCF resulted in a protective effect. Maximal NK activity towards HCL was obtained when the target tumour cells were separately precultured with dCF and the NK-enriched effectors precultured with dCF + IFN-alpha. The effect of dCF and IFN-alpha was also measured using the standard K562 cells as targets for NK activity. dCF enhanced NK activity following preculture of both effector and target K562 cells, but IFN-alpha did not reduce K562 cell susceptibility to NK lysis as it did for HC cells. Our findings suggest that (a) dCF and IFN-alpha, which are used to treat HC, could function via activation of NK cells, (b) effects on both effector and tumour target cells should be taken into account, and (c) caution should be exercised in extrapolating the effects of NK-cell activity against K562 cells to those on HC targets.

Cytotoxicity, Immunologic↗
PubMed1990

Effects of gamma-interferon on DR antigen expression, growth, 3,5,3'-triiodothyronine secretion, iodide uptake, and cyclic adenosine 3',5'-monophosphate accumulation in cultured human thyroid cells.

We have examined, using the same system of human thyroid cells in culture, the effects of the cytokine human gamma-interferon (gamma IFN) on the expression of DR antigen, cell pro-liferation, cAMP accumulation, and the differentiated functions, iodide uptake and T3 secretion. gamma IFN elicited a dose- and time-dependent increase in DR expression, with a maximum effect on day 5 of culture. The cytokine, at the same concentrations and experimental conditions as those found to be effective in inducing DR antigen expression, caused on day 5 of culture a dose-dependent inhibition of [3H]thymidine incorporation, DNA content, cell count, as well as TSH-stimulated (but not basal) iodide uptake and T3 secretion. The gamma IFN suppressive influence on the differentiated functions was not merely due to a reduction in cell number, but was also apparent when results were expressed per micrograms DNA. Since the cytokine did not inhibit TSH- or forskolin-stimulated cAMP accumulation and showed a suppressive influence toward 8-bromo-cAMP- and forskolin-stimulated T3 secretion, its inhibitory effect seems to be exerted at a site located distal to cAMP formation. Although gamma IFN alone was devoid of any effect on cAMP accumulation, it enhanced forskolin-stimulated (as well as TSH-activated) cAMP in the presence of 3-isobutyl-1-methylxanthine, an inhibitor of cAMP degradation. Thus, it would seem that gamma IFN also exerts an influence on cAMP formation (rather than degradation) at a step subsequent to TSH binding to its receptor. The effects we observed seem specific to gamma IFN, since alpha IFN, although capable of inhibiting human thyrocyte multiplication, lacked any influence on DR antigen expression, cAMP accumulation, or T3 secretion by human thyroid cells. In what way, if any, is gamma IFN-induced DR antigen expression on human thyrocytes, an event believed to be critical in the pathophysiology of autoimmune thyroid disease, related to decreased thyroid function and growth is presently unknown.

Cell Count↗
PubMed1989

Decreased natural killer (NK) activity in patients with myeloproliferative disorders.

Natural killer (NK) cell number and activity were measured in 26 patients with myeloproliferative disorders and the results were compared with 16 age-matched control patients. The percent of Leu-11b-positive cells was 11% +/- 3% in the patients, compared with 12% +/- 4% in the control patients. Ten of 26 patients, however, had NK activity lower than all of the control values at three different effector to target cell ratios (E:T) (P less than 0.005). The values of those patients with low unstimulated NK activity remained low despite stimulation with interleukin-2 (IL-2) or alpha-interferon (alpha-IFN), whereas the values of those patients with normal unstimulated activity responded to IL-2 and alpha-IFN like the control patients. Three of the ten patients with low NK activity had a history of malignant neoplasms. None of the 16 patients with normal NK activity had a history of malignant neoplasms (P less than 0.05). We conclude that patients with myeloproliferative disorders frequently have low endogenous NK cell activity in vitro. The dysfunction of the NK system appears to be intrinsic because the relative number of NK cells was similar to control values and the response to stimulation with IL-2 and alpha-IFN was suboptimal. There may be a relationship between low NK activity and the development of malignant disease in such patients.

Bloodletting↗
PubMed1989

Increase in the suppressor-inducer T cell subset in multiple myeloma and monoclonal gammopathy of undetermined significance.

The expression of CD4 (helper-inducer), CD8 (suppressor-cytotoxic) and CD4 subpopulations (2H4 and 4B4) were studied in patients with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS) and in healthy controls. The percentages of CD4+ cells and CD8+ cells among total T cells were not different between the three groups studied. However the percentage of CD4+ cells of the suppressor-inducer type (CD4 + 2H4 +) was 53 +/- 9% in patients with MGUS, and 51 +/- 9% in those with MM, compared to 46 +/- 5 in the controls (P = 0.033 and P = 0.07 respectively). A significant negative correlation between serum polyclonal IgM and the percentage of CD4 + 2H4 + cells was found in patients with MM but not in those with MGUS. No difference was found in the percentage of CD4 + 4B4 + (helper CD4+ cells) between the various groups. These findings suggest that the elevation of the suppressor-inducer subset occurs prior to clinical manifestations of MM, perhaps as an immune response to the malignant clone. The existence of elevated proportions of CD4 suppressor-inducer cells was associated with the hypogammaglobulinaemia observed in patients with MM. Since no hypogammaglobulinaemia was present in those with MGUS, additional factors are needed to explain the influence of the CD4 + 2H4 + cells on the production of immunoglobulins.

Aged↗
PubMed1989

Immature cells identified by the H-1 hematology analyzer predicts thymidine incorporation after mitogenic stimulation.

The incorporation of thymidine by lymphocytes stimulated by phytohemagglutinin (PHA) was correlated with the number of immature cells identified by the Technicon H-1 as blasts. The number of blasts and thymidine incorporation plateaued on day 3. At that time, a high linear correlation between the two variables was found (r = 0.949, p less than 0.01). The H-1 evaluated the samples in 60 seconds as compared to 3 hours of processing required to calculate thymidine incorporation. We conclude that the number of immature cells identified by the Technicon H-1 can predict the degree of thymidine incorporation after stimulation of peripheral blood cells with PHA. The H-1 may replace the more time consuming and dangerous use of radioactive thymidine incorporation in evaluating patients' functional immunologic status.

Blood Cell Count↗
PubMed1988

Impaired autologous mixed lymphocyte reaction (AMLR) in patients with ataxia-telangiectasia and their family members.

We used the autologous mixed lymphocyte reaction (AMLR) to test T cell function in four patients with Ataxia-telangiectasia (AT), in 11 first-degree relatives and in 20 controls. There was a marked reduction of AMLR in the patients and in three relatives compared to the age-matched controls. In the AT patients the defect in AMLR was intrinsic to the CD4 subpopulation, since exogenous IL-2 did not improve the response of isolated CD4 cells. In contrast to normal controls, pre-incubation of autologous B cells with Epstein-Barr virus (EBV) did not enhance the reduced AMLR in the AT patients and the three first-degree relatives. We conclude that in both patients with AT and in some of their family members there is an intrinsic defect in CD4 T cells. This defect leads to diminished reactivity to EBV infected autologous B cells, and may explain in part the high incidence of malignancies observed in such families.

Ataxia Telangiectasia↗
PubMed1988

Discordant effect of interferon on natural killer activity and tumor cell sensitivity to lysis in hairy cell leukemia.

We studied the action of alpha-interferon (IFN) and interleukin-2 (IL-2) on natural killer (NK)-rich fractions and autologous tumor cells from two patients with hairy cell leukemia (HCL). The addition of IFN or IL-2 to the NK-rich fractions resulted in a significant increase in NK activity against the autologous tumor cells. This stimulatory effect was blocked if the target hairy cells (HCs) were preincubated with either IFN or IL-2. Pretreatment of the HCs with anti-Tac antibody entirely prevented the blocking effect of IL-2 and partially the blocking effect of IFN. One patient was treated with recombinant alpha c-IFN. After 2 months there was a dramatic reduction in the number of HCs in the peripheral blood coincident with the loss of the protection effect of IFN against NK lysis of the patient's HCs. NK activity against autologous tumor cells correlated poorly with that against the K562 cell line. We conclude that there is a discordant effect of IFN and IL-2 on NK activity and HC sensitivity to lysis. The Tac receptor appears to play a role in this sensitivity. Caution should be exercised in extrapolating the effects of NK activity against K562 cells to those on HC targets.

Antineoplastic Agents↗
PubMed1986

Does stem cell self renewal and progenitor cell commitment operate through an effector-memory cell mechanism?

We propose a model for stem cell self renewal and transition into commitment towards a variety of cell lineages. In this model the production of both "effector cells" (as represented by the mature cells in the different cell lineages) and of progenitor "memory" lymphocytes, takes place concomitantly. The experimental evidence supporting this model is as follows: Pure lymphocytic suspensions (PLS) are established and persist in culture when nude mouse-spleen and lymph-node cells are maintained on X-irradiated fibroblast monolayers in the presence of the S-phase cytotoxic agent cytosine arabinoside (Ara-C). From these PLS the following colony types can be initiated by the corresponding inducing (stimulating) factors (CSF): histiocytes (tissue macrophages) - CSF-1; granulocytes-macrophages (GM) - CSF-GM; mast cells - MMSF; granular-NK mucus secreting cells - IL-2; and multilineage colonies - IL-3. Mitotically active blast cells (formed by transformation of lymphocytes), condense into motile small cells when the stimulatory factor is removed. These "memory" lymphocytes are committed as they carry the receptors for the specific CSF; they respond by retransformation into blast cells. A dramatic increase in mast-cell colony forming cells is found in bone marrow, spleen and lymph-nodes of mice infected with Schistosoma mansoni. By maintaining PLS with both Ara-C and each of the CSFs and then titrating the incidence of CFC in the residual PLS, we find that each one of the CSFs acts on an independent set of cells in the PLS to produce the corresponding colony type. Finally, the concept suggests that the various blast cells carrying the receptors, undergo condensation into memory lymphocytes when dissociated from the environment prevailed by the corresponding CSF. In this way pluripotential blast-cells condense into motile lymphocytes which are committed to pluripotentiality.

Animals↗
PubMed1985

Granular natural-killer cells develop into mucus-secreting cells.

Colonies of granular natural-killer cells selectively develop in lymph-node cell cultures of nude mice after stimulation with rat T-cell growth factor. When these cells are grown on X-irradiated monolayers prepared from 16-18-day-old mouse embryos, they are triggered to synthesize and secrete a sulphated glycoprotein that can be identified as mucus. As a result of an erosive process of the granules, the mucoid material accumulates in pools in the cytoplasm matrix. The secretion is operated through a process of budding of double-membrane-bound vesicles. The successful triggering of mucous synthesis is interpreted by the successful growth of those mesenchymal cells in the embryonic monolayer that function in the induction of epithelial morphogenesis in the developing embryo.

Animals↗
PubMed1983

Murine interleukin-2 generates glycogen-rich and mucus-secreting NK cells.

Colonies of cells termed 'giant granular leucocytes' (GGL) displaying natural killer (NK) activity were generated in cell culture. The prominent feature of these cells was the formation of large cytoplasmic pool--the 'theca'--filled up with glycogen. This was demonstrated by the strong positive red staining of the theca with periodic acid Schiff reagent (PAS) which was abolished by prior treatment with amylase. Two different procedures were employed for obtaining colonies of NK-GGL. In the first, mice were injected either with killed Corynebacterium parvum or with killed Bordetella pertusis preparations and their mesenteric lymph-node cells were grown on syngeneic X-irradiated embryonic skin fibroblast monolayers. At the foci of GGL formation the fibroblasts were killed and the cleared areas thus formed were populated by adherent GGL. In the second procedure, supernates from rat or mouse spleen cultures stimulated with concanavalin A (Con A)--Interleukin-2 (IL-2)--were added to cultures of spleen and lymph-node cells prepared from either ordinary or from athymic nude mice. Richest GGL populations developed when rat IL-2 was added to cells of nude mice. Mouse IL-2 was less consistent. With nude mouse cells it stimulated, either mast cells or GGL, or both; rat IL-2 did not stimulate mast-cell differentiation in nude mouse cultures. In contrast, supernates from lymph-node cell cultures prepared from mice infected with Schistosoma mansoni. Mucosal mast cell-stimulating factor (MMSF) stimulated the formation of colonies of mast cells but not GGL. When MMSF was added as late as 23 days, colonies of young mast cells appeared and mast cells progressively increased in number. When rat IL-2 was added to such mature mast-cell cultures on the 30th day, colonies of cytolytic-GGL appeared. These observations indicate that precursors of mast cells and GGL persist in the cultures and preserve their potential to be stimulated by T-cell factors. GGL-NK cells developed on monolayers prepared from whole embryos released substance that displayed morphology and staining characteristic of mucus. Evidence gathered from in-vitro and in-vivo studies links the in-vitro GGL-NK cells to motile cells that inhabit the mucosal epithelium. Based on the observations, a hypothesis on the function of NK cytotoxicity is brought forward. It proposes the replacement of ordinary epithelial cells, which are killed during a proliferative and differentiative response of other cells at the onset of an infection course.

Amylases↗