Natural cell-mediated cytotoxicity in normal human peripheral blood lymphocytes and its in vitro boosting with BCG

Abstract

Natural cell-mediated cytotoxicity (NCMC) against K-562 human erythroleukemic cells was monitored in an overnight chromium release assay using normal human peripheral blood lymphocytes (PBL) as effective cells. Two hundred and ten normal individuals were tested from 3 to 24 times over a period of 3 years. The level of NCMC was shown to vary from 4% to 46% lysis at an effector-to-target cell ratio of 5/1; males had higher levels of activity than females (P less than 0.001). A group of individuals with low natural killer (NK) cell activity (below the 90% tolerance limit) was identified in replicate experiments and 60% of them were young women (ages 20--39). In vitro boosting of NK activity with Bacillus Calmette-Guérin (BCG) was also studied; overall, 56% of normal individuals responded positively to BCG. There was a significant (P less than 0.001) correlation between the unstimulated level of NCMC and the in vitro boosting with BCG, as 63% of individuals with a normal level of NK activity could be boosted as against only 19% of persons with low NK activity. We have also established the in vivo relevance of this in vitro test by determining the degree of correlation between responses to in vitro boosting with BCG and a positive or negative reaction in a hypersensitivity skin test using 5 IU of PPD (purified protein derivative of BCG). Our results indicate that NCMC is an individual trait that varies little under physiological conditions, and that the response to BCG is a characteristic property of the effector lymphocyte, depending primarily on the unstimulated level of NCMC.

NK Cell Activity and Estrogen Hormone Levels during Normal Human Pregnancy

“…[5], and confirmed by other authors [13][14][15][16]. However, depression of NK activity did not reach significance in all of the reports [13,14], This could be due to the great individual variability of NK activity in healthy populations [4,13,17] which makes it necessary either to use large experimental groups or to apply longitudinal (individual), instead of cross-section analy sis. The result of our follow-up study, al though obtained with a relatively small num ber of probands, has clearly shown a signifi cant decrease of NK activity towards the end of pregnancy.…”

“…The suppressive effect of p-estradiol on the activity of NK cells in mice was first reported by Seaman et al [1], Estrogeninduced NK activity suppression was accom panied by an increased metastatic spread [2], In women with high estrogen levels, an in creased chance of breast cancer development was recorded, which was attributed to low levels of NK activity [3], A slightly, but sig nificantly lower level of NK activity was also found in healthy women in generative age, in comparison to that of healthy men [4], and explained as a consequence of sex steroid hormone influence [4]. This implies that NK activity is not only regulated by supraphysiological concentrations of estrogens, as shown in animal experiments [1], but also by the physiological ones.…”

Influence of ovarian hormones on urogenital infection

“…Oestrogen receptors have also been identified on lymphoid cells, 9 thymic cells, [9][10][11] and mononuclear cells in peripheral blood. 7 Natural killer (NK) cell activity is reported to be lower in women than in men 12 and may be decreased by the use of oral contraceptives 13 and during pregnancy as oestrogen levels rise. 14 Although physiological doses of oestrogens have no eVect on NK activity in vitro, [15][16][17] oestrogen treatment of castrated and normal mice produces a significant decrease in NK activity in spleen and lymph nodes.…”

In vitro enhancement of human natural cell-mediated cytotoxicity by purified influenza virus glycoproteins

“…PBL from normal healthy male donors (20 to 45 years of age) were treated with carbonyl iron to remove monocytes and macrophages and then layered on a Ficoll-Hypaque density gradient (Pharmacia Fine Chemicals, Uppsala, Sweden). Washed PBL were adjusted to a concentration of 4 x 106 viable cells per ml (as assessed by trypan blue exclusion) with RPMI-1640 (GIBCO Laboratories, Grand Island, N.Y.) supplemented with 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 4 mM L-glutamine, 10% heat-inactivated fetal bovine serum, and antibiotics as described previously (23).…”