István Láng

Effector activity of OKT4+ and OKT8+ T-cell subsets in lectin-dependent cell-mediated cytotoxicity against adherent HEp-2 cells

The role of OKT4+ and OKT8+ T-cell subsets was studied in lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC was evaluated by detachment from the monolayer of [3H]thymidine prelabeled HEp-2 cells in a 24-hr assay with a concanavalin A (Con A) dose of 25 microgram/ml at effector:target cell ratios of 5:1, 25:1, and 50:1. Under these conditions but without Con A considerable natural cell-mediated cytotoxicity (NCMC) was not elicited; however, the cytotoxicity was significantly augmented in the presence of Con A (=LDCC) by sheep erythrocyte rosette-forming T lymphocytes and by both OKT4+ and OKT8+ T-cell fractions. LDCC activity by isolated OKT8+ T cells was superior to that by OKT4+ T cells and unfractionated T lymphocytes. By contrast, addition of either OKT4+ or OKT8+ T cells together with unfractionated T lymphocytes, or OKT4+ and OKT8+ T cells mixed at ratios of 1:1, 1:2, and 2:1, to target cells did not result in major differences in comparison of LDCC activities by these mixed effector cell populations with each other or with that by unfractionated T lymphocytes. Parallel studies were carried out to determine the effect of OKT4+ and OKT8+ T-cell subsets on the Con A-induced proliferation of peripheral blood mononuclear cells (PBMC). While OKT8+ T cells inhibited the mitogenic response to Con A, OKT4+ T lymphocytes had no major effect. A higher responsiveness of the OKT8+ to OKT4+ T-cell subset in LDCC to HEp-2 targets and in Con A-induced lymphocyte proliferation is suggested.

Ketoconazole in vitro inhibits mitogen-induced blastogenesis, antibody-dependent cellular cytotoxicity, natural killer activity and random migration of human leukocytes

Ketoconazole at concentrations of 1-10 micrograms/ml dose dependently inhibits mitogen-induced blastogenesis, antibody-dependent and spontaneous cytotoxic (natural killer) activity of human lymphocytes and random migration of human leukocytes. Lectin-dependent cytotoxic activity is not affected by the drug.

Effect of in vivo and in vitro treatment with dialyzable leukocyte extracts on human natural killer cell activity

Abstract The effects of in vivo and in vitro treatment with human dialyzable leukocyte extracts (DLE) on natural killer (NK) cell activity were studied in 12 patients with malignancies in an allogenic test system using K-562 target cells. A marked increase in NK cell activity was observed in 7 patients with originally low cytotoxic capacity, while originally normal NK cell activity of other tumor patients and of healthy subjects was not significantly influenced by DLE treatment. The observed stimulation of NK cell activity by DLE may be a possible mechanism of its therapeutic effects.

Depressed natural and lectin-dependent cell-mediated cytotoxicity against adherent HEp-2 cells in patients with systemic lupus erythematosus.

Natural cell-mediated cytotoxicity /NCMC/ was evaluated using human adherent 3H-thymidine-prelabelled HEp-2 epipharynx carcinoma cells as targets at 50:1 effector-target cell ratio in a 24 hr assay. For lectin-dependent cell-mediated cytotoxicity /LDCC/ studies cultures contained also 25/micrograms/ml concanavalin A /Con A/. Peripheral blood mononuclear cells /PBMC/ of nine patients with active systemic lupus erythematosus /SLE/ failed to exert NCMC or LDCC against HEp-2 targets. In contrast, an increased adherence /decreased detachment from the monolayer/ of HEp-2 target cells was observed in the presence of PBMC from SLE patients that was further promoted by the addition of Con A during LDCC assay.

Depressed lectin-dependent cell-mediated cytotoxicity against adherent HEP-2 cells in patients with carcinoma of the uterine cervix

SummaryLectin-dependent cell-mediated cytotoxicity of peripheral blood mononuclear cells from patients with uterine cervix carcinoma was evaluated using human adherent 3H-TdR-prelabeled HEp-2 epipharynx carcinoma cells as targets at a 50:1 effector-target cell ratio with 25 ώg concanavalin A/ml in a 24-h assay. Peripheral blood mononuclear cells from 13 patients with cervical carcinoma in stage IV failed to exert cytotoxicity against HEp-2 targets. In contrast, an increased survival (decreased detachment from the monolayer) of HEp-2 cells was observed in the presence of peripheral blood mononuclear cells from patients, this being significantly enhanced by addition of concanavalin A during the lectin-dependent cell-mediated cytotoxicity assay.

Decreased antibody-dependent and spontaneous cell-mediated cytotoxicity in patients with chronic renal failure.

Antibody-dependent and spontaneous lymphocytotoxicity of blood mononuclear cells from 15 patients with chronic renal failure was studied in allogeneic K-562 and xenogeneic chicken erythrocyte test systems. Both antibody-dependent and spontaneous cytotoxic activities were significantly decreased in uremic patients as compared to the corresponding mean values of healthy control persons and non-uremic patients with the same underlying diseases. The addition of autologous serum further reduced the impaired cytotoxic capacity of uremic lymphocytes. Uremic sera also inhibited the antibody-dependent and spontaneous lymphocytotoxicity of healthy individuals.

Effects of therapy with dialyzable leukocyte extracts containing transfer factor activity on antibody-dependent cytotoxic activity in humans

Abstract The effects of therapy with dialyzable leukocyte extracts (DLE) containing transfer factor on antibody-dependent cellular cytotoxicity (ADCC) were studied in 10 patients in a xenogeneic test system using chicken erythrocytes as target cells. A marked increase in “K” cell activity was observed in 4 patients with originally low cytotoxic capacity, while originally normal ADCC activity was not significantly influenced by DLE treatment. The changes in cytotoxicity were not accompanied by parallel increase in the total Fc-receptor-bearing cell population. The observed stimulation of ADCC by DLE may be a possible mechanism of its therapeutic effects in diseases where ADCC plays a role.

Effect of haemodialysis on the antibody-dependent and spontaneous cell-mediated cytotoxicity of patients with chronic renal failure.

Antibody-dependent and spontaneous lymphocytotoxicity of blood mononuclear cells from 10 patients with chronic renal failure was studied before and after haemodialysis in xenogeneic chicken erythrocyte and allogeneic K-562 test systems. The originally impaired antibody-dependent and spontaneous lymphocytoxicity of uraemic patients significantly improved following haemodialysis. Both pre- and post-haemodialysis uraemic sera strongly inhibited the antibody-dependent and spontaneous cytotoxicity of autologous and of healthy control lymphocytes.

Effect of Fc receptor blocking on human natural and lectin-dependent cell-mediated cytotoxicity against adherent HEp-2 cells

The effect of Fc receptor (FcR) blocking by aggregated human gamma-globulin (AGG) was studied on natural (NCMC) and lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. Cytotoxicity was measured by detachment from the monolayer of [3H]TdR-prelabelled HEp-2 cells. LDCC was evaluated in a 24 h assay at 50:1 effector-target cell ratio in the presence of 25 micrograms/ml concanavalin A (Con A). Under these conditions but without Con A considerable NCMC was not elicited by normal lymphocytes. FcR blocking by AGG treatment of effector cells resulted in a significant NCMC activity to HEp-2 targets. In contrast, AGG treatment profoundly depressed LDCC. Monocyte depletion of effector cells had no major influence on the effect of AGG on NCMC and LDCC activities. An interference of FcR blocking by AGG and LDCC in response to Con A is suggested.