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S Targan

Publications and source records attributed to S Targan.

48 records · Page 3Linked to original sources

Interferon activation of "pre-spontaneous killer" (pre-SK) cells and alteration in kinetics of lysis of both "pre-SK" and active SK cells.

Interferon augments spontaneous killer cellular cytotoxicity (SKCC). This modulation may be vital in both tumor resistance and host viral defenses. To date, whether increased numbers of effector cells or activation of individual effector cells is responsible for this augmentation has not been established. Using a single cell assay where SK killing is directly visualized by the reading of trypan blue uptake at various time points by effector-target cell conjugates plated in agarose gel, we measured in vitro alterations in percentage of conjugate formation, number of active SK cells, and kinetics of SK cell lysis at the single cell level after 1 hr of interferon incubation. After interferon, there is no difference in number of cells that bind K-562 targets. This augmentation of cytotoxicity is due to both recruitment of new effector cells and an activation of the lytic process of both the new and already active SK cells.

Analysis of Variance↗

A single cell marker of active NK cytotoxicity: only a fraction of target binding lymphocytes are killer cells.

The frequency of cytotoxic NK cells has been directly measured. The cytotoxic assay is performed by preparing conjugates of effector cells bound to target cells and assessing under the microscope target cell lysis by the trypan blue dye exclusion test. With Ficoll-Hypaque purified cells, it was found that 11--13% of lymphocytes formed conjugates with K562 or Molt-4 target cells, but only 3--4% of the total lymphocytes actually killed. Thus, the NK cell's ability to bind targets cannot be equated to the ability to kill. The nature of the noncytotoxic binding lymphocytes is discussed. The kinetics of lysis by NK cells show a random distribution of killing in relationship to time and plateaus at 3--4 hours. The frequency of killing is the same for a wide variety of populations tested at different times. We conclude that some of the target binding cells are antigen specific NK cells that can be converted to cytotoxic natural killer cells.

Cell Line↗

In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity.

The present work shows that stimulation of peripheral blood lymphocytes with autologous or allogeneic B-cell lines leads to a strong induction of cytotoxic effector cells with spontaneous killer (SK) cell specificity, apart from the specific response directed against the particular stimulating cell. To demonstrate this we have determined a relative target cell specificity in the SK system, defined by the short-term 51Cr release assay, and established a relative specificity index (RSI). Using this approach we have been able to show that killer cells induced during a 5-day cocultivation period with B-cell lines have a similar PSI to that of unstimulated SK cells. In addition, we have shown that such killer cells can be induced from several different lymphocyte subpopulations and that they, in contrast to SK cells, do not express Fc receptors. The implications of these findings in relation to the nature, mechanism, and biological significance of the SK cell system is discussed.

B-Lymphocytes↗

Spontaneous and lectin-dependent cellular cytotoxicity by lymphocyte subpopulations against cell lines susceptible or resistant to spontaneous cytotoxicity.

In the present study we have investigated whether cell lines, which are resistant to spontaneous cytotoxicity, can be killed by lectin-dependent cellular cytotoxicity (LDCC), the expression of EAC (7S) receptors on LDCC effector cells, and the relationship between spontaneous cytotoxicity and LDCC when EAC (7S) receptor-positive or -negative subpopulations are tested against different target cell lines. We found that target cells which are resistant to spontaneous cytotoxicity can, indeed, be killed by LDCC, and that there is an inverse relationship between spontaneous cytotoxicity and LDCC, both when unfractionated lymphocytes were tested against different target cells and when fractionated cells were tested against cell lines highly susceptible to spontaneous cytotoxicity. The implications of these findings, in relation to the relative specificity of the spontaneous cytotoxicity system, are discussed.

Cell Line↗

Mechanism of inhibition of natural killing by a glycopeptide isolated from the K562 plasma membrane.

The mechanism of lysis by cytotoxic T lymphocytes, K cells, and natural killer (NK) cells is imperfectly understood at this point. In this report, material (glycopeptide) isolated from the plasma membranes of K562 cells and fractionated on lectin affinity adsorbents which has been shown to inhibit NK lysis, was used in several specific NK assays to ascertain what stages of the NK-lytic sequence is inhibited by this substance. Results indicate that this glycopeptide (a) does not inhibit initial binding, but dissociates conjugates following initial effector target interactions; (b) inhibits NK lysis beyond Ca-dependent programming, and (c) inhibits lysis induced by NK cell-derived soluble cytotoxic factors (NKCF) in a soluble factor assay. These results suggest that this glycopeptide can effect the lethal hit stage of NK lysis and may represent structures which can associate directly with NKCF.

Binding, Competitive↗