Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes.

The in vitro effects of the recreational drugs, ethanol (EtOH) and nicotine, on natural killer (NK) antibody-dependent cellular cytotoxic (ADCC) and lymphokine-activated killer (LAK) cell activities on normal lymphocytes were investigated. Lymphocytes precultured with EtOH at concentrations of 0.4 and 0.6% (v/v) produced significant suppression of NK and ADCC activities. In target-binding assays, EtOH decreased the target-binding capacity of effector cells. EtOH also inhibited the activities of Percoll-separated, NK-enriched large granular lymphocytes. EtOH-induced inhibition of NK activity could be reversed by incubating lymphocytes for 1 hr with interferon. The generation and lytic capacity of LAK cells was also significantly depressed by EtOH when added at the initiation of culture. Nicotine at concentrations of 5 and 10 micrograms/ml, when added directly to mixtures of effector and target cells, produced significant inhibition of NK activity. Nicotine (2 micrograms/ml) and EtOH (0.01, 0.1, and 0.2%) at noninhibitory concentrations when added separately, showed significant suppression of NK activity when used in combination. Pretreatment of target cells with either EtOH or nicotine for 4 hr did not affect cytotoxic activity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or nicotine showed normal 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrate that EtOH and nicotine have significant immunomodulatory effects on the cytotoxic activities of human lymphocytes which may be of clinical relevance.     

Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients

The relative effects of azathioprine (AZA) and prednisone (PRED) on natural killer (NK) activity and the antibody-dependent cellular cytotoxicity (ADCC) of K (killer) cells and the number of FcR and other lymphoid cells were examined in renal transplant recipients. In addition to both long-term (>6 months) and short-term (<6 months) transplant recipients receiving conventional AZA-PRED therapy, an important group of long-term recipients receiving PRED but not AZA was studied for the first time. Both NK activity and ADCC are profoundly reduced in the long-term AZA-PRED group but are normal in the long-term PRED-alone (no-AZA) group. The short-term AZA-PRED group exhibits NK and ADCC levels significantly lower than normal but not as low as those of the long-term AZA-PRED group. Patient groups with low NK and ADCC also have low circulating Fc receptor-bearing (FcR) cells. A single patient in the long-term AZA-PRED group was removed from AZA therapy, and approximately 3 months was required for the patient's suppressed NK and ADCC to return to normal. These findings indicate that AZA rather than PRED is the major drug important in suppressing ADCC and NK activity in renal transplant recipients. Several months are required for combination AZA-PRED therapy to reduce these cytotoxic activities. Similarly, several months are required for suppressed ADCC and NK activity to return to normal upon discontinuation of AZA.     

Role of prolactin in the modulation of NK and lak cell activity after short- or long-term morphine administration in neoplastic patients

In a previous work we demonstrated that chronic in vivo antalgic therapy of cancer patients with morphine reduced the endogenous cytotoxic activity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to investigate the mechanisms by which morphine affects NK and LAK cell function further, we evaluated the modulation exerted by short- or long-term morphine administration on either NK/LAK cell cytotoxicities or plasma levels of prolactin (PRL) and other immunomodulating neurohormones. An intravenous morphine injection (10mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug injection in neoplastic patients. The administration of bromocriptine before the injection of morphine prevented both PRL augmentation and the increase in LAK cell activation, although it did not prevent the inhibition of NK cytotoxicity. The chronic oral administration of morphine (90±30mg/day for 1 month) also resulted in higher PRL levels; the NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The plasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long-term experiments. The absolute number and the percentages of lymphocyte populations, as well as the percentage of IL-2 receptors, were not modified after short-term morphine administration whereas little changes of T lymphocyte populations and NK cell number were observed after oral treatment with morphine. In vitro morphine did not affect the development of LAK cell activity. In conclusion, our findings indicate that morphine reduces NK cytotoxicity and increases the development of LAK cell cytotoxicity after short- and long-term administration. The effect of morphine on LAK cell activation but not on NK cell reduction is related to the modulation of PRL levels determined by the opioid drug.     

Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin.

Natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxic functions can be strongly augmented by the iron-carrier protein lactoferrin (LF). LF significantly enhances NK and LAK activities when added at the beginning of NK or LAK cytotoxicity assays. LF is effective in augmenting cytotoxic activities at concentrations as low as 0.75 microgram/ml, and higher concentrations of LF induce greater augmentation of NK and LAK. Iron does not appear to be essential for LF to increase NK and LAK, as depleting iron from LF with the chelator deferoxamine does not affect the capacity of LF to increase cytotoxicity. LF is known to have RNase enzymatic activity, and LF enhancement of NK and LAK can be blocked by RNA. However, LFs from two different sources with over 100-fold difference in RNase activity are equally effective in enhancing NK and LAK. Furthermore, purified non-LF RNase does not modulate NK or LAK activity and DNA is as effective as RNA in blocking LF augmentation of NK or LAK cytotoxicity. Therefore, the RNase activity is unlikely to be responsible for LF enhancement of the cytotoxicities. Newborn infants are known to have low NK activity and NK and LAK cells have been implicated in host defense against microbial infections. Thus, maternal milk-derived LF may have a role in boosting antimicrobial immunity in the early stages of life. In adults, LF released from neutrophils may enhance NK and LAK functions in the inflammatory process induced by microbial infections.     

Natural killer cell activity in the rat. VI. Characterization of rat large granular lymphocytes as effector cells in natural killer and antibody-dependent cellular cytotoxic activities

The present study examined rat natural killer (NK) cells, which mediate not only NK activity but also antibody-dependent cellular cytotoxicity (ADCC). NK and ADCC activities were compared with regard to organ distribution, strain distribution, Percoll fractionation of the effector cells, effects of aging, and potential to be augmented by biological response modifiers (BRM). Like NK activity, appreciable ADCC activity was observed in peripheral blood leukocytes (PBL), splenic leukocytes (SPL), and peritoneal exudate cells (PEC), but not in cell preparations from the peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), bone marrow (BM), and thymus (THY). ADCC activity, when compared with NK activity, was significantly higher in PBL but the same or lower in SPL and PEC. In terms of strain distribution, a high NK/ADCC strain (rnu/rnu), four intermediate NK and high ADCC strains (PVG/RTLRL, Lewis, PVG/OLA, and F344), an intermediate NK/ADCC strain (WF/N), and a low NK/ADCC strain (Buffalo) were observed. Fractionation of effector cells on discontinuous Percoll gradients revealed that both NK and ADCC activities were associated with relatively high-density large granular lymphocytes (LGL). In contrast, ADCC but little or no NK activity was associated with lower density LGL. However, the NK activity of this lower-density LGL population could be elicited following the in vitro incubation with a number of BRM, including rat interferon (IFN) and OK-432, but not rat interleukin-2 (IL-2). In general, the ADCC activity of both higher and lower density LGL-enriched cell populations correlated with both the frequency of FC gamma R+ LGL and the percentage of LGL binders to antibody-coated P815 target cells. The present study also has shown that in contrast to NK activity, which remained relatively stable with age, ADCC activity from F344 but not WF/N rats increased until 30-50 wk of age. This increase of ADCC activity in older F344 rats was accompanied by an increase in the percentage and absolute number of lower density FC gamma R+ LGL. This study demonstrates a number of similarities and differences between NK and ADCC activities in the rat. These findings should be useful for further examining and comparing the in vivo development and biological role of these two effector arms of the immune system.     

In vitro effect of alpha-interferon on mononuclear cells of normal and autoimmune patients

The effect of lymphoblastoid interferon (IFN-alpha) on cell-mediated and humoral immunity was studied in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The base-line natural killer (NK) and antibody dependent cytotoxic cell (ADCC) activity was higher than normal in individuals with RA. The NK and ADCC activities were tested after IFN-alpha pretreatment and the augmentation of NK and ADCC activity was less in these patients than in normals. Lymphoblastoid IFN inhibited antigen induced T-cell proliferation in SLE to a lesser extent than in normal individuals. Finally, the addition of lymphoblastoid IFN was also less effective at suppressing in vitro polyclonal antibody formation by mononuclear cells from patients with SLE than from normals, with enhancement observed in some patients at the lower IFN-alpha concentrations tested.     

Human T Lymphocyte Clones: Influence of Culture Conditions and Optimization of Proliferative Assays

Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment of the human natural killer (NK) target cells Molt-4, Jurkat, and U937 reduced their susceptibility to killing by human NK cells in a dose-dependent fashion. This indicates that a cell surface structure, anchored by a glycosyl-phosphatidylinositol (G-PI) moiety, is important in NK cytotoxicity. In contrast, another common NK target cell line, K562, remained susceptible to NK killing after enzyme treatment, suggesting that distinct target structures are expressed by this cell line. PI-PLC treatment of Molt-4 cells also reduced their sensitivity to human lymphokine activated killer (LAK) cells, suggesting that NK and LAK cells share common specificity in the killing of Molt-4. In contrast, PI-PLC had no effect on the killing of the LAK target cell line, Daudi, which is only weakly sensitive to unactivated NK cells. Killing of a variety of murine target cells by murine NK cells was not affected by PI-PLC treatment, but cross-species killing of Molt-4 by murine NK cells was inhibited by PI-PLC, suggesting a common mechanism in the killing of this human target cell line. The PI-PLC treatment of effector cells from either species did not reduce their NK activity. The reduction in sensitivity of the Molt-4, Jurkat, and U937 target cells probably results from a loss of a target specific G-PI linked membrane molecule, but other possible explanations for these results are also discussed.     

Interleukin-4 differentially regulates interleukin-2-mediated and CD2-mediated induction of human lymphokine-activated killer effectors.

Natural killer (NK) cells can be differentiated into lymphokine-activated killer (LAK) effectors following stimulation with interleukin (IL)-2. This induction can be negatively regulated by IL-4. In this study, we demonstrate that the stimulation of NK cells through the CD2 pathway with (9-1 + 9.6) monoclonal antibodies can also induce these cells to secrete tumor necrosis factor-alpha (TNF-alpha) and to differentiate into LAK effectors. More importantly, our data indicate that, in contrast to the IL-2-induced LAK generation, the anti-CD2-triggered LAK activity was not regulated by IL-4. IL-4 was found to enhance the LAK activity as well as NK cell proliferation following activation with anti-CD2 by a mechanism involving, at least in part, an increased TNF-alpha production. Using immobilized monoclonal antibodies against the Fc receptor (Fc gamma RIII or CD16) for NK stimulation, we also observed that the anti-CD16-induced LAK activity was not inhibited by IL-4. These data further point to a pivotal role of TNF-alpha as a regulatory cytokine in anti-CD2-induced LAK generation, and suggest that IL-4 could serve as a discriminatory factor between two distinct pathways involved in the activation of non-MHC-restricted cytotoxicity.     

Dissociation of natural killer and lymphocyte-activated killer cell lytic activities in human CD3− large granular lymphocytes

CD3^? large granular lymphocytes (LGL) are known to display natural killer cell (NK) activity without prior sensitization or restriction by major histocompatibility antigens. Upon short-term exposure to interleukin-2, NK cells were shown to acquire lymphocyte-activated killer cell (LAK) activity. The aim of this study was to analyze the characteristics of these lytic activities. Our data indicated that both NK and LAK activities were Ca²⁺ dependent; however, they could be dissociated by a Ca²⁺ channel blocker or a Ca²⁺ channel competitor agent. Moreover, NK activity was associated with granule exocytosis of lytic proteins spontaneously present in CD3^? LGL, the most likely candidate being the pore-forming protein perforin. By contrast, LAK activity was found to be dependent on de novo protein synthesis and distinct from granule exocytosis. Our results strongly suggest that NK and LAK activities could be defined as two distinct pathways involving different lytic mediators.     

Generation of natural killer cells and lymphokine-activated killer cells in human AB serum or fetal bovine serum

Interleukin 2 (IL-2) can induce or enhance the cytotoxic activity of natural killer (NK) cells and lymphokine-activated killer (LAK) cells. The effects of fetal bovine serum (FBS) and human AB serum (HABS) on the IL-2-induced NK cell and LAK cell activities of large granular lymphocytes (LGL) were measured, respectively, against the NK-sensitive cell line K562 and the LAK-sensitive cell line Daudi. FBS and HABS were essentially equivalent in their effects on IL-2-dependent NK activity with prolonged culture. However, with prolonged incubation from 1 to 5 days of PBMC in the presence of IL-2, there was considerably less generation of LAK cell activity in FBS (Day 3: 5.3 +/- 3.4 LU/10(7) cells) compared to HABS (Day 3: 44.6 +/- 4.2 LU/10(7) cells) (P less than 0.05). These differences in IL-2-dependent LAK cell generation did not appear to be due to the lot of the FBS or to activating factors present in individual samples of HABS. Similarly, the suppressive effects of FBS could not be reversed with increasing concentrations of IL-2 ranging from 10 to 100 U/ml. Importantly, the presence of FBS in the cultures resulted in more cell death (15.9 +/- 5.6%) at 4 days of culture compared to HABS (1.8 +/- 1.0%) (P less than 0.05). These results suggest that FBS may inhibit generation of LAK effector cells, but not NK cells in cultures containing IL-2 and that the use of HABS as a culture supplement is preferable to FBS in studies of human LAK cell function.     

Ontogeny of natural killer cell activity and antibody dependent cell mediated cytotoxicity in pigs

Cells from pigs of various ages were collected from peripheral blood, mesenteric lymph node, spleen and thymus and their ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell activity was determined. ADCC against chicken red blood cell (CRBC) was present in cells from peripheral blood, lymph node and spleen, but was absent in thymic cells. There were no age-related differences in ADCC to CRBC and cells from fetal pigs had similar activities to cells from adult pigs. Maximal cytotoxicity against CRBC was found in the polymorphonuclear leukocyte (PMN) cell fraction. In contrast to the good response against CRBC, PMN cells were not lytic in the ADCC assay when PI3 virus-infected cells were used as target cells. Peripheral blood lymphocytes (PBL) had low but significant lytic activity against PI3 virus-infected cells in the presence of high concentrations of specific antiserum. NK cell activity against K562 target cells was readily detected in PBL of pigs older than 2 weeks but was not observed with cells from spleen, lymph node or thymus from pigs of any age. PBL of pigs younger than 2 weeks of age had low but detectable NK activity: however, fetal pigs had no NK activity against K562 target cells. In contrast, when PI3 virus infected Vero cells were used as target cells, NK cells were detected in spleen and PBL, but not lymph nodes or thymus, of pigs greater than one day of age. Similar to the absence of activity to K562, none of the lymphoid cells from fetal pigs had NK activity against PI3 virus-infected Vero cells. The present results suggest that the effector cells that mediate ADCC are distinct from those that mediate NK activity in that cells mediating ADCC develop earlier and are found in different organs than the NK cells. Additionally, the cells that mediate NK activity against viral infected cells may be different from those that mediate NK activity for K562 target cells; however, regardless of the target, NK cells are not present before birth in the pig.     

Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases

This overview summarizes current knowledge on the overall efficacy and potential contribution of antibody-dependent cellular cytotoxicity (ADCC) and lymphokine-activated killer cell (LAK) activities in evoking non-major histocompatibility complex (non-MHC) cytolytic responses to human immunodeficiency virus-1 (HIV-1)-infected targets. High titers of ADCC antibodies to the HIV-1 virion are present in HIV-1-seropositive populations at all stages of disease. These antibodies are broadly reactive with a large number of HIV-1 strains and are predominantly directed against envelope determinants spanning both gp120 and gp41. However, the relative ability of natural killer (NK) effectors, derived from HIV-seropositive individuals, to evoke ADCC responses becomes increasingly impaired with disease progression. HIV-1-seropositive individuals also show marked decreases in both production of and responsiveness to interleukin-2 (IL-2). HIV-1-seropositive individuals generally have the ability to generate ex vivo propagated LAK cells; however, these cytolytic effectors are less effective than their counterparts derived from healthy controls. Increased understanding and control of non-MHC-restricted cytotoxic-responses to HIV, and their induction by lymphokines, may lead to improved treatment strategies for the management of AIDS and related diseases.     

Prothymosin α1 modulates lymphokine-activated killer cell activity and IL-2 production by peripheral blood lymphocytes from melanoma patients in vitro

The effects of prothymosin α1 (Pro α1) on the natural killer (NK), lymphokine (IL-2)-activated killer (LAK) cell activity and the phytohaemagglutinin (PHA)-induced IL-2 secretion of peripheral blood T-lymphocytes (PBL) from 34 malignant melanoma patients of all clinical stages were studied in vitro. On average, melanoma patients showed lower NK and LAK cell activities than healthy donors. In particular, patients with metastases revealed an impaired NK cell activity. However, individuals showed a broad range of LAK cell sensitivity to Pro α1 depending, among other factors, on the disease stage. LAK cell activities were not correlated to tumour stage. Patients' impaired LAK cell activity could be restored by Pro α1. Only patients at stage II (regional metastases) responded to Pro α1. The IL-2 secretion from PBL melanoma and healthy donors did not differ; Pro al administration was without any significant effect. However, stage III (distant metastases) PBL expressed significantly lower IL-2 levels, compared to stage I (primary tumours). The highest IL-2 level was found to be associated with tumour stage II. Pro al enhanced the IL-2 secretion from stage I PBL. Therefore Pro α1 administration abrogated the defective LAK cell activity and IL-2 secretion of PBL, mainly from patients at early melanoma stages.     

Dual role of TNF-alpha in NK/LAK cell-mediated lysis of chronically HIV-infected U1 cells. Concomitant enhancement of HIV expression and sensitization of cell-mediated lysis

The U937-derived chronically HIV-infected U1 cell line and uninfected U937 cell clones were efficiently lysed by both unstimulated (NK) and IL-2-stimulated (lymphokine-activated killer; LAK) peripheral blood mononuclear cells (PBMC) of healthy HIV-seronegative donors. Pretreatment of target cells with IFN-gamma down-modulated killing of both U1 cells and two U937 cell clones, and up-regulated MHC class I expression. In contrast, TNF-alpha enhanced the sensitivity of infected U1 cells, but not of U937 cell clones to NK / LAK cell lysis. Co-cultivation of IL-2-stimulated PBMC with U1 cells triggered expression and replication of HIV by cell-cell contact, and this effect was inhibited by anti-TNF-alpha antibodies (Ab); virus production was partially inhibited by zidovudine. Of interest, anti-TNF-alpha Ab protected U1 cells from LAK cell activity. Thus, TNF-alpha can induce HIV expression from chronically infected U1 cells, but also plays an important role in sensitizing these cells to lysis.     

Lymphokine-activated killer cells and aging in mice: significance for defining the precursor cell

The present study was undertaken to define the cell populations which mediate lymphokine-activated killer (LAK) cell activity in mice. Because old mice exhibit markedly decreased to nondetectable natural killer (NK) cell activity, this age-associated change provided an advantageous system to examine the contribution of NK and T cells to LAK activity. Spleen cells from either young (6-9 weeks) or old (20-26 months) mice were cultured with 1000 units/ml of recombinant interleukin 2 (rIL 2) for 3-5 days. The cells were then tested in a 51 Cr-release assay for their cytotoxicity against NK-resistant fresh tumor cells (MCA-102). The LAK activity exhibited by spleen cells from old mice following 5 days of culture was equivalent to that developed by spleen cells of young mice. This result was contrary to what would be anticipated if mature NK cells comprise the primary precursors of LAK activity, and required further elucidation. The Thy-1 and asialo GM1 (ASGM1) phenotypes of LAK precursor and effector cells were therefore examined by depletion techniques using the appropriate antibodies plus complement. The results using spleen cells harvested after 5 days of culture with rIL 2 showed that LAK effector cells which developed from spleen cells of both young and old mice were predominantly Thy-1+ (85.3% young; 91.8% old) and some coexpressed ASGM1. Spleen cells were treated prior to culture to study the precursor cells. Development of LAK activity by spleen cells from both young and old mice was greatly reduced by pretreatment with anti-ASGM1 plus complement. However, since spleen cells of old mice exhibit very low mature NK activity, these data suggest that the LAK precursors, at least in old mice, may be ASGM1+ NK precursor cells rather than mature ASGM1+ NK effector cells. In addition, treatment with anti-Thy-1 plus complement inhibited generation of a significant proportion of LAK activity only in the spleens of old mice, suggesting a qualitative difference in LAK precursor cells with age and supporting the heterogeneity of the cells which are capable of developing LAK activity.     

Differential cytokine regulation of natural killer cell-mediated necrotic and apoptotic cytotoxicity.

Natural killer (NK) cells can kill target cells by either necrotic or apoptotic mechanisms. Using the 51Cr-release assay to measure necrotic death of target cells, neonatal NK cells had low NK activity (K562 targets) and high lymphokine-activated killer (LAK) activity (Daudi targets) compared with adult cells, as has been previously reported. Using a 125I-deoxyuridine (125I-UdR) release assay, cord cells were shown to also have higher apoptotic LAK activity against YAC-1 target cells. Interleukin-4 (IL-4) inhibited interleukin-2 (IL-2)-induced necrotic killing of target cells by adult effectors but had no such inhibitory effect on cord cells. In contrast, IL-4 inhibited both adult and cord LAK cytotoxicity of YAC-1 target cells by apoptotic mechanisms with higher suppression observed in cord cell preparations. Using a colorimetric substrate conversion assay, IL-2 induced higher, and IL-4 had a more significant suppressive effect on, cord cell granzyme B enzyme activity compared with adult cells, paralleling apoptosis cytotoxicity data. Co-culture of either adult or cord LAK cells with IL-4 had a similar inhibitory effect on granzyme B protein expression, as detected by Western blotting. In contrast, IL-4 did not inhibit perforin expression, thereby defining IL-4 as a cytokine that can differentially regulate the NK cell-mediated cytotoxicity processes of apoptosis and necrosis. The differential sensitivity of cord cells to cytokine regulation of cytotoxicity may also have implications for cord blood transplantations, as NK cells are known to function as an effector cell in both graft-versus-host disease and in the graft-versus-leukaemia phenomena.     

慢性乙肝患者杀伤性免疫细胞功能的研究

通过对４４例病毒性肝炎患者Ｔ细胞亚群，ＮＫ细胞活性与ＬＡＫ细胞活性的观察，探讨了在慢性乙型肝炎病毒复制与非复制状态下的杀伤性细胞活性。结果表明：在乙肝病毒的高复制状态下，ＣＤ８＾＋细胞数增加，ＣＤ４＾＋／ＣＤ８＾＋比例显著下降；ＮＫ细胞活性与ＬＡＫ细胞活性也明显低下，且在ＨＢｅＡｇ与ＨＢＶＤＮＡ阳性组中，ＮＫ活性与ＬＡＫ活性的改变与ＨＢｅＡｇ的Ｐ／Ｎ值变化呈显著负相关，而ＮＫ活性与ＬＡＫ活性变化则     

Natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities can be differentiated by their different sensitivities to interferon and prostaglandin E1

Though purported to be identical cells (or in identical populations of cells), the natural killer (NK) cell mediating spontaneous natural cytotoxicity and the killer (K) cell mediating antibody-dependent cellular cytotoxicity (ADCC) may not be totally identical, at least in susceptibility to regulation by the immunomodulators prostaglandin E₁ (PGE₁) and interferon (IFN). We demonstrate here that NK cells are always enhanced by IFN, while K cells are inhibited from binding targets, resulting in fewer effectors at optimal concentrations of antibody. Only at 10- to 100-fold suboptimal concentrations of antibody is ADCC activity enhanced. As measured by magnitude of inhibition and dose-response titration, ADCC activity is less sensitive to the effects of PGE₁ than is NK activity in the⁵¹Cr release assay and single-cell assay. After overnight incubation with or without PGE₁, whatever sensitivity ADCC activity had to PGE₁ is lost. However, NK cells incubated in the presence of PGE₁ overnight are still sensitive to inhibition. Indomethacin boosts NK activity without having any effect on ADCC activity. Finally, NK activity is substantially reduced by overnight incubation of cells at room temperature, which has no effect on K cells.     

Clinical Progression of HIV Infection: Role of NK Cells

The authors determined the natural killer (NK) and lymphokine-activated killer (LAK) activities of peripheral blood mononuclear cells (PBMCs) from a severely immunocompromised (CD4 cell counts <100/mm³) group of AIDS patients, using K562 and U937 target cells. An increase in cytotoxicity was observed in the PBMCs of all 17 patients following a 48 h incubation with the combination of 400 U/ml of recombinant gamma interferon plus 20 U/ml of natural interleukin-2. Although NK and LAK activities were significantly higher in healthy controls than in patients, patients' LAK activity was higher than the NK activity of controls. The authors also demonstrated that the use of medium containing fetal bovine serum, when compared with medium containing autologous serum, increases NK activity without affecting LAK activity. Lymphokine augmentation of cytotoxicity is achievable in severely immunocompromised AIDS patients and might be of benefit in delaying opportunistic infections and malignancies.