Peripheral Blood Natural Killer Activity Research Articles

Intratumoral Injection of Dendritic Cells Engineered to Secrete Interleukin-12 by Recombinant Adenovirus in Patients With Metastatic Gastrointestinal Carcinomas

To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy.

Intravenous Immunoglobulin Inhibits Natural Killer Cell Activity In Vivo in Women With Recurrent Spontaneous Abortion

We previously reported elevation of natural killer (NK) cells in women with recurrent spontaneous abortion (RSA) of immune etiology. In this study, we investigated the effect of intravenous immunoglobulin G (IVIg) on peripheral blood NK activity in vivo in women with RSA. Blood was drawn prior to and 7-11 days after IVIg therapy in eight women with RSA. NK activity was measured using K562 as target cells for 51Cr-release assays. Serum IgG concentrations were also measured. All received 400 mg/kg/day of IVIg for 3 consecutive days. 1) Seven of eight women became pregnant. Five delivered a live born infant. Three out of five women (60%) who delivered a live born infant showed a significant inhibition of NK cytotoxicity post IVIg and the rest did not show any changes; 2) NK cytotoxicity was significantly increased in a woman who miscarried again; 3) A woman who miscarried a chromosomally abnormal fetus showed a significant inhibition of NK cytotoxicity after IVIg; and 4) Serum IgG concentration increased significantly from 9.3 +/- 3.0 mg/ml to 23.5 +/- 5.1 mg/ml post IVIg therapy. IVIg effectively inhibits peripheral blood NK activity in vivo. These results are consistent with our previous finding showing that IVIg inhibits NK cell activity in vitro. Women with RSA and elevated NK cells may benefit from IVIg treatment.

Anti-Metastatic Activity Induced by the In Vivo Activation of Purified Protein Derivative (PPD)Recognizing Thl Type CD4 + T Cells

The Th1 type CD4 + T cell clone (MH2), which is capable of recognizing purified protein derivative from Mycobacterium tuberculosis (PPD), was examined for its anti-metastatic activity against melanoma. In using an in vitro proliferative assay, MH2 was able to recognize PPD-derived antigen in a major histocompatibility complex class 11-restricted manner. MH2 showed neither any natural killer (NK) activity nor cytolytic activity against syngeneic B16 melanoma. This clone produced interferon-γ, tumor necrosis factor and interleukin-2, but not interleukin-4, when co-cultured with PPD and irradiated syngeneic C57BL/6 spleen cells, suggesting that this clone could thus be assigned to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10 6 MH2 and 50μg PPD increased the NK activity of the peritoneal exudate cells (PEC) and the percentage of NK1.1 + cells in the PEC. These activated NK cells showed a low but significant cytolytic activity against B16 melanoma. The augmented NK activity induced by the co-injection of MH2 and PPD was maintained by the weekly additional i.p. injections of PPD alone. Using a murine metastatic model, an i.p. co-injection of MH2 and PPD-induced antimetastatic activity against B16 melanoma. This anti-metastatic activity was then abrogated by the in vivo administration of anti-asialo GMt serum. In addition, the NK activity in both peripheral blood and metastatic lungs was significantly augmented in the mice which were co-injected with MH2 and PPD. Taken together, these findings indicate that the in vivo activation of Tht type CD4+ T cells augmented the NK activity in vivo and thus could potentially be an efficient immunotherapeutic weapon against metastasis of melanoma. These results also imply that adoptive immunotherapy could induce antimetastatic activity through cytokine production but not through any direct cytolytic activity.

Electrical Stimulation of the Dorsal Midbrain Periaqueductal Gray Suppresses Peripheral Blood Natural Killer Cell Activity

This study examined the effects of dorsal midbrain periaqueductal gray (PAG) stimulation on both splenic and peripheral blood natural killer (NK) cell function as well as the proliferative response of lymphocytes to phytohemagglutinin mitogen. Male Sprague-Dawley rats were implanted with bipolar electrodes in the dorsal PAG. Following recovery, bipolar electrical stimulation eliciting a flight response was delivered at the rate of one/min for 30 min to freely moving rats. While dorsal PAG stimulation did not alter mitogen response or splenic NK activity, stimulation of this region of the PAG produced a marked decrease in peripheral blood NK response. In order to begin to explore a possible mechanism regulating suppression of peripheral blood NK activity, naltrexone (10 mg/kg) was administered prior to dorsal PAG stimulation. The results of this experiment replicated the findings that demonstrated suppression of peripheral blood NK following dorsal PAG stimulation. Naltrexone did not effect PAG induced suppression of peripheral blood NK. These findings point to the importance of the dorsal aspect of the PAG in the regulation of peripheral blood NK activity and further suggest that this phenomenon may not be opioid mediated.

Catecholamines induce alterations of distribution and activity of human natural killer (NK) cells.

Catecholamines have been suggested to be responsible for altered cellular immunity after stress. This study was performed to determine the effects of adrenaline and noradrenaline on lymphocyte subpopulations and NK cell functions. Subjects were given a subcutaneous injection of either NaCl, adrenaline (5 micrograms/kg), or noradrenaline (10 micrograms/kg). Catecholamine concentrations, subsets of peripheral blood lymphocytes, NK activity, and antibody-dependent cellular cytotoxicity (ADCC) were analyzed before (baseline) and 5, 15, 30, 60, and 120 min after injection. There were no differences between groups in the distribution of CD2+ and CD8+ lymphocytes over time. However, CD3+ and CD4+ T cells decreased significantly 5 to 60 min after injection of adrenaline. In contrast, NK cell numbers (CD16+, CD56+) increased significantly 5 min after injection of adrenaline and noradrenaline, reached the highest values 15 to 30 min postinjection, and subsequently declined to baseline values 60 (noradrenaline) and 120 (adrenaline) min, respectively, after injection. Similar alterations for NK activity and ADCC were observed after administration of both catecholamines. These data suggest that both sympathetic-adrenal hormones are similarly potent modulators of natural immunity and provide further evidence that catecholamines might be responsible for the observed alterations in immune functions after phases of acute stress.

Central corticotropin-releasing hormone reduces cellular immunity

Corticotropin-releasing hormone (CRH) acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to those observed after stress. A reduction of splenic natural killer (NK) activity has also been described following the central administration of CRH. In this study, we examined whether other in vitro measures of cellular immunity, including peripheral and splenic NK activity, lymphocyte responses to mitogen stimulation, and numbers of splenic T and NK cell subpopulations, are altered following CRH. Synthetic rat CRH (1.0 μg) microinjected into the lateral ventricle reduced splenic and peripheral blood NK activity, lymphocyte responses to mitogenic stimulation, and percentage of splenic NK cell numbers. Numbers of splenic lymphocytes and T cell subpopulations were not altered by central CRH. These findings suggest that central CRH acts to reduce a number of in vitro cellular immune measures similar to the effects of inescapable stress.

Inhibitory effect of granulocyte-macrophage colony-stimulating factor therapy on the generation of natural killer cells

We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on the natural killer (NK) cell lineage in patients with aplastic anemia and myelodysplastic syndrome. Selected bone marrow (BM) cells were prepared by the elimination of nylon wool-adherent cells and mature T and NK cells from BM cells. The frequency of BM NK progenitors relative to BM cells selected was significantly decreased 4 weeks after the start of rhGM-CSF therapy (P less than .01), while the peripheral blood NK cell count and NK activity were also significantly decreased (P less than .05). A return to the pretreatment levels was seen 4 weeks after the cessation of treatment in all cases. No suppressive effect was noted in the patients who received rhG-CSF therapy. These results suggest that rhGM-CSF therapy suppresses the generation of NK cells from human BM NK progenitors.

Inhibitory Effect of Granulocyte-Macrophage Colony-Stimulating Factor Therapy on the Generation of Natural Killer Cells

Abstract We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on the natural killer (NK) cell lineage in patients with aplastic anemia and myelodysplastic syndrome. Selected bone marrow (BM) cells were prepared by the elimination of nylon wool-adherent cells and mature T and NK cells from BM cells. The frequency of BM NK progenitors relative to BM cells selected was significantly decreased 4 weeks after the start of rhGM- CSF therapy (P less than .01), while the peripheral blood NK cell count and NK activity were also significantly decreased (P less than .05). A return to the pretreatment levels was seen 4 weeks after the cessation of treatment in all cases. No suppressive effect was noted in the patients who received rhG-CSF therapy. These results suggest that rhGM- CSF therapy suppresses the generation of NK cells from human BM NK progenitors.

Analysis of Immunologic Mechanisms of High Natural Killer Cell Activity in Tuberculous Pleural Effusions

We found natural killer (NK) activity to be high in tuberculous pleural effusions from which Mycobacterium tuberculosis was cultured. In this study, we investigated and compared the mechanisms of this NK activity in tuberculous pleural effusions and peripheral blood. Cytotoxicity was augmented in tuberculous pleural effusion mononuclear cells (PEMNC) and peripheral blood mononuclear cells (PBMNC) by culture with purified protein derivative (PPD). Prior to culture with PPD, there were many more interleukin-2 receptors (IL-2R, p55) on Leu 11+ (CD16+) cells in tuberculous PEMNC than in tuberculous PBMNC. After 5 days of culture with PPD, the numbers of IL-2R increased in both PEMNC and PBMNC. PPD-induced cytotoxicity was inhibited by the addition of anti-IL-2R monoclonal antibody (anti-IL-2R mAb). Interferon-gamma (IFN-gamma) production was abundant in the supernatants of cultured tuberculous PEMNC and PBMNC, but very little interleukin-2 (IL-2) and IFN-alpha and -beta were produced. Considerably more IFN-gamma was produced in tuberculous PEMNC than in tuberculous PBMNC, and PPD-induced cytotoxicity was inhibited by anti-IFN-gamma monoclonal antibody (anti-IFN-gamma mAb). Cell surface analysis after PPD-induced cytotoxicity was performed by complement-mediated cytolysis. Leu 11+ cells exhibited essential cytotoxicity in the induction and effector phases, but neither OKT4+ (CD4+) nor OKT8+ (CD8+) cells displayed such cytotoxicity. These data suggest that Leu 11+ cells in tuberculous PEMNC are activated by M. tuberculosis through IFN-gamma and that IL-2R plays an important role in the activation of NK cells.

Effects of splenectomy on the development of tumor-specific immunity

We have previously reported on the antimetastatic effects of experimental adoptive immunotherapy using plastic adherent lymphokine-activated killer cells (ALAK) cells (R. E. Schwarz et al. Cancer Res. 49: 1441, 1989). We have also reported that the spleen is a superior source of lymphocytes for A-LAK cell generation (R. E. Schwarz and J. C. Hiserodt, Med. Hypotheses 28: 165, 1989). This study, therefore, was designed to examine the effects of splenectomy itself on tumor growth in an experimental animal model. Natural killer (NK)-resistant MADB106 mammary adenocarcinoma cells were injected iv into F344 rats to generate multiple lung metastases. Splenectomies (Sx) were performed on Days −6, −3, −1, 0, 1, 3, 6, and 10, counted from the time of tumor injection. Groups consisted of six animals each, and shamanesthetized and -operated animals served as controls. Splenectomies, if performed between Days −3 and +1, had significant antitumor effects as documented by the number of outgrowing surface metastases (5 ± 7 vs >300; P < 0.0001) and by animal survival (>100 vs 21 ± 3 days; P < 0.001). However, splenectomies, performed at an earlier or later stage, did not show these effects. Sx did not alter peripheral blood NK activity or the percentages of mononuclear cell subsets except for a slight decrease in the T-helper/T-suppressor ratio ( P < 0.04). Interleukin 2 (rhIL2), given at 2.5 × 10 5 U/kg/day for 3 days immediately after splenectomy, completely abrogated the observed antitumor effects. Subcutaneous tumor rechallenge of long-term surviving animals showed no tumor take in 87% of the animals. We conclude that the development of tumor-specific immunity in this model is facilitated, if splenectomy is performed during a critical interval, and is abrogated by IL2 administration. Splenectomy can show significant immunomodulatory and/or therapeutic effects in tumor-bearing individuals.

Host environment as a modulating factor of swine natural killer cell activity

The large granular lymphocyte (LGL) population includes such heterologous effector cells as the natural killer (NK), lymphokine activated killer (LAK), antibody dependent cellular cytotoxic (ADCC) and non-MHC restricted T cells. These LGL subpopulations have all been associated with NK activity. In some species, enhanced NK activity is correlated with exposure to viral, bacterial and parasitic agents. Consequently, the host environment could serve as a modulatory factor of NK activity in laboratory animals. During our investigation of tumor regression in melanoma swine, we observed marked differences in the NK activity of peripheral blood lymphocytes collected from two separate groups of Sinclair melanoma miniature swine maintained under different conditions. Group A pigs were vaccinated and extensively treated for endo- and ectoparasites while group B swine were not. In addition, chronic exposure to infectious and parasitic diseases have been documented in the group B swine. Peripheral blood NK activity was assessed by standard in vitro 4-h chromium release assays. The NK activity of group B swine was markedly exaggerated when compared to group A swine. Thus, the significance of NK activity may be distorted as a result of the modulating effect of pathogen exposure.

Natural Killer Cell Function in Patients With Acquired Immunodeficiency Syndrome and Related Diseases

This review describes current knowledge of changes in natural killer (NK) cell function in acquired immunodeficiency syndrome (AIDS)-related disorders, vis-à-vis associated abnormalities in NK cytolytic function, NK cell subset distribution, NK cytopathology, and lymphokine regulation. NK cells, which are closely associated with large granular lymphocytes, are spontaneously cytotoxic to tumor and virally infected targets. As such, they may play a role in natural resistance to human immunodeficiency virus type 1 (HIV-1)-associated disorders and other opportunistic infections. Yet, peripheral blood NK activity is frequently reduced in patients with HIV-1-induced disease. NK cells are heterogeneous both with respect to their expression of serologically defined membrane antigens and functional activity. In AIDS-related syndromes, there appears to be a diminution of the NK pool (CD16+ cells) involved in cytolytic function, while there is an elevation of the NK pool that coexpresses NK (Leu 7+) and T (CD8+) cell markers, which show little or no involvement in cytolytic function. The impairment of in vitro NK function is not associated with a reduced frequency of lytic conjugates of effectors and target cells nor with the recycling capacity of these effector cells but rather is associated with defects in the NK cell lytic machinery following formation of such conjugates. NK cells in AIDS patients show an impairment in effector cell microtubule rearrangement following target cell interaction. The causes of NK cell dysfunction in AIDS-related disorders remain unknown. NK cells do not appear to express the CD4 epitope of the HIV receptor, nor have they been demonstrated to be susceptible to infection by HIV-1. There appears to be a preponderance of immature NK cells and a lymphokine imbalance in patients with HIV-1 associated disease. Interleukin-2 can partially restore diminished in vitro NK function. Elucidation of the involvement of the NK compartment in natural resistance to HIV-1 merits further investigation.

Natural killer (NK) activity of peripheral blood and regional lymph nodes in patients with genitourinary malignant tumors. 2. NK activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes

We investigated natural killer (NK) activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes in order to examine the host's defence mechanisms against cancer. The materials were obtained from 26 patients with genitourinary cancer and 9 patients with benign diseases, who were used as controls. NK activity was measured by ATP-chemiluminescence (ATP) assay, a new method which is well correlated to the 51Cr-release assay, and T-lymphocyte subsets were stained with anti-Leu-2, -3, -4, -7, and -11 monoclonal antibody. The NK activity of regional lymph nodes was lower than that of the peripheral blood in all 35 cases, and the percentage of Leu 7+ and Leu 11+ cells was in agreement with that of the NK activity detected by ATP assay. In the peripheral blood, the percentage of Leu 3+ cells was lower in high stage patients than it was in low stage patients and controls, but in the regional lymph nodes it was paradoxically higher. The NK activity of regional lymph nodes against autologous tumor cells was low in 8 patients with bladder cancer. It appears from this study that the regional lymph nodes have no function as immunological barriers for metastasis and we therefore conclude that they should be dissected during surgery.

Natural killer cell activities of patients with breast cancer against different target cells.

Natural killer (NK) cell activity against K 562 erythroleukemic- and MCF-7 breast carcinoma-derived cells was monitored in short-term (3 h/K 562) and long-term (18 h/MCF-7) chromium release tests for 60 patients with untreated primary breast disease. Target cell lysis was the same for patient groups with benign (n = 13) and malignant (n = 47) breast disease (27% versus 36% mean chromium release; target:effector ratio 40:1 for K 562 and 28% versus 40% for MCF-7 cells). NK activity as defined by short-term lysis of K 562 cells did not correlate with MCF-7 cell lysis in long-term assays for the carcinoma patients. This functional heterogeneity of natural cytotoxic activities of breast cancer patients was confirmed by a different age distribution for K 562 and MCF-7 cell lysis and high levels of MCF-7-directed NK activity in the grade I tumor group (56.2%). Our results indicate that measurement of peripheral blood NK activity against a breast carcinoma-derived cell line (MCF-7) defines a disease-related natural cytotoxic activity which correlates better with prognostic tumor parameters (tumor grading) than NK activity as defined by the lysis of K 562 erythroleukemic cells. NK activity testing against breast carcinoma cell lines should be used to monitor natural cytotoxic activities in breast cancer patients and its modulation by different routes of treatment.

Distribution of natural killer cells and lymphocyte subclasses in Jessner's lymphocytic infiltration of the skin and in cutaneous lesions of discoid and systemic lupus erythematosus.

We studied the cell infiltrates in biopsies from lymphocytic infiltration of the skin (LIS), with six monoclonal T cell antigen-specific antibodies and compared the reactivity pattern with those in biopsies from discoid and systemic lupus erythematosus skin lesions and allergic contact skin reactions. A newly described antibody (NK9) recognizing natural killer (NK) cells and activated cytotoxic T lymphocytes was included, and the numbers and activity of circulating NK cells was determined. Immunohistochemical staining revealed that the numbers of NK9-positive cells were highest in LIS. The distribution of T lymphocytes (OKTII + ve), helper T cells (OKT4 + ve), suppressor T cells (OKT8 + ve), Langerhans cells (OKT6 + ve) and activated T cells (anti-Tac + ve) in LIS differed from those in DLE,SLE and allergic contact reactions. However, the number of circulating NK cells (large granular lymphocytes) and the NK activity in peripheral blood were normal in LIS. We conclude that in LIS a distinct type of T cell activation occurs; the cause of this remains to be determined.

Natural killer activity in patients with chronic hepatitis treated with OK432, interferon, adenine arabinoside and glycyrrhizin.

Natural killer (NK) activity in the peripheral blood of patients with chronic liver disease was measured using 51Cr labeled K562 cells as target cells. NK activity was elevated but not significantly in patients with chronic hepatitis compared with healthy controls and significantly lower in the patients with hepatocellular carcinoma. The activity decreased in the order of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the level of NK activity in patients with chronic hepatitis did not correlate with the level of alanine aminotransferase (ALT), it tended to be elevated in association with elevation of ALT in patients treated with OK432, interferon-beta, glycyrrhizin or adenine arabinoside. In chronic liver disease, phytohemagglutinin (PHA) skin test showed a positive correlation with NK activity. In all patients who were treated with the immunopotentiator, OK432, and whose HBeAg became negative, NK activity was elevated during the treatment. These results suggest that the NK activity in peripheral blood may be related to hepatocytic injury even if this is not the effector mechanism of the injury.

Phenotypic heterogeneity and recycling capacity of natural killer cells in normal human pregnancy

Natural killer (NK) cells have the ability to kill a variety of target cell types and the possibility that such cells could mount an effective attack on the developing fetus has not been discounted. The present study extends previous work showing that maternal NK reactivity against K562 target cells (TC) is reduced during pregnancy. Here we demonstrate using cytotoxicity assays at both the population and single cell level that, although depressed in number, maternal NK cells exhibiting the capacity to kill K562 TC are as lytically active in their ability to recycle and destroy multiple TC as NK cells from non-pregnant females. Moreover, two colour immunofluorescence analysis of the NK cell-associated markers Leu-7 and Leu-11b indicates that, in addition to a reduction in the absolute number of TC conjugate-forming cells, pregnant females present in their peripheral blood a larger proportion of TC-binding Leu-7 +11 − cells. These cells may be lytically immature. Small changes in NK cell profile and activity in maternal peripheral blood may be indicative of much more significant changes at the feto-maternal interface. It is, however, clear that pregnant females retain a population of highly active NK cells, thus minimising the possibility of immunocompromise.

Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia.

Peripheral blood natural killer (NK) activity in patients with B-cell chronic lymphocytic leukemia (B-CLL) is frequently low or absent. Because cimetidine (a histamine-2 antagonist) has been shown to alter human lymphocyte function in vitro, we decided to study cimetidine's effect on peripheral blood NK activity of patients with B-CLL and controls. We administered cimetidine orally (1.2 gm per day) to seven patients with B-CLL and 12 controls for up to 28 days. Peripheral blood NK activity of patients with B-CLL rose from a pretreatment level of 0.7 +/- 0.5 (mean +/- SEM) lytic units/10(6) cells (LU) to 8.7 +/- 2.4 LU (P less than 0.05) at day 28. Peripheral blood NK activity of controls decreased after 14 days of cimetidine treatment but returned to pretreatment levels by day 28. When peripheral blood cells from controls were exposed to cimetidine during in vitro incubation (10 micrograms/ml), mean NK activity was increased at 48 hours (54% +/- 22% increase over controls, n = 5, P less than 0.05). Single cell cytotoxicity assays revealed increased killing of target cells (but not effector-target conjugation) with cimetidine-exposed effector cells. These data suggest that cimetidine may be useful to augment peripheral blood NK activity for patients with B-CLL.

Modulation of spontaneous immunoglobulin production by natural killer cells in rheumatoid arthritis.

Synovial fluid (SF) mononuclear cells obtained from patients with rheumatoid arthritis (RA) spontaneously produce large amounts of immunoglobulin. In the rheumatoid joint, natural killer (NK) cell activity is reduced in comparison with that in the peripheral blood (PB). We examined the ability of SF NK cells to modulate the spontaneous production of Ig in RA SF, and we contrasted this with the activity in PB from RA patients and from normal subjects. We found that the spontaneous production of IgG was greater in RA SF than in RA or normal PB. The baseline NK activity was significantly lower in RA SF than in RA or normal PB (P less than 0.005). Incubation with anti-Leu-11b and complement reduced NK activity in PB, but not in SF, and it significantly (P less than or equal to 0.021) increased IgG production in both RA SF and RA PB. Lysis of NK cells in this manner also resulted in a significant increase (P less than 0.02) in IgM production in RA SF. These results suggest that NK cells with a Leu-11b phenotype down-regulate the ongoing synthesis of IgG and IgM in the rheumatoid joint.

Natural immunity against ovarian tumors

We have analysed natural killer (NK) cytotoxic activity in peripheral blood and ascitic fluids of patients with advanced stage of ovarian epithelial carcinoma. All patients displayed low NK activity in peripheral blood and virtually no cytotoxicity in ascitic fluids. NK activity in ascitic fiuids could be substantially augmented after regional administration of virus-modified tumor cell extracts (VMTE), and that in peripheral blood after culture of effector cells with interleukin-2 (IL-2) in vitro. Activated NK cells displayed cytotoxic activity against NK-sensitive and NK-resistant tumor cell lines as well as against fresh ovarian tumors. Parallelism was found between regional NK augmentation and regression of malignant ascites. The latter observation suggests possible NK cell role in defense against ovarian tumors.