ABSTRACT
Cytotoxic and suppressor activity of decidual cells lymphoid population were analysed in 14 women with normal pregnancy and labour, in 8 women with light pre-eclampsia and 11 women with early and premature rupture of amniotic sac. In late stages of pregnancy decidua is characterised by high suppressor activity of the lymphoid cell population. In early and premature rupture of amniotic sac suppressor activity of decidual cell lymphoid population was significantly decreased.
Subject(s)
Decidua/immunology , Lymphocytes/immunology , Pregnancy/immunology , Cytotoxicity Tests, Immunologic , Decidua/cytology , Female , Humans , Lymphocytes/cytology , Obstetric Labor, Premature/immunology , Obstetric Labor, Premature/pathology , Pre-Eclampsia/immunology , Pre-Eclampsia/pathology , Pregnancy Trimester, ThirdABSTRACT
Bispecific heteroconjugated F(ab')2 fragments were prepared from pepsin-digested monoclonal OKT3 (anti-CD3) and 3G8 (anti-CD16) antibodies with 5,5'-dithiobis- (2-nitrobenzoic acid). When these bispecific antibodies (BsA) were added to peripheral blood lymphocyte (PBL) cultures with 100 U/ml human recombinant interleukin-2 (rIL-2), preferable growth of natural killer cells occurred. After 3 weeks the frequencies of CD56+ and CD56+3- cells in cultures with BsA were 74 +/- 7% and 65 +/- 7%, respectively, compared with 48 +/- 6% and 29 +/- 7% in control cultures. The frequencies of CD3+ lymphocytes in the presence of BsA, cells from 1-day cultures were labelled with fluorescein isothiocyanate (FITC)-conjugated anti-CD3, CD4 and CD8 monoclonal antibodies (mAb) and propidium iodide which stains dead cells. Flow cytometry revealed that more than 95% of the dead cells in cultures with BsA were CD3+. Thirty-seven per cent of CD3+, 43% of CD4+ and 17% of CD8+ cells were dead on day 1, and after 3 days the CD4+/CD8+ ratio among viable lymphocytes was 1.6 in the control and 0.5 in BsA cultures. Taken together, these results show that bispecific (anti-CD3 x anti-CD16) F(ab')2 fragments are strongly immunomodulatory by inducing the killing of T cells by CD16+ cells.
Subject(s)
Antibodies, Bispecific/immunology , CD3 Complex/immunology , Killer Cells, Natural/immunology , Receptors, IgG/immunology , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , CD3 Complex/analysis , CD4 Antigens/analysis , CD56 Antigen , CD8 Antigens/analysis , Cell Division/immunology , Cell Survival/immunology , Cells, Cultured , Humans , Interleukin-2/immunology , Recombinant Proteins/immunologyABSTRACT
Interleukin-2 (IL-2)-induced generation of non-major histocompatibility complex (MHC)-restricted killer cells among human cord blood lymphocytes (CBL) was investigated. After 1 week in culture with recombinant (r)IL-2 and human serum (HuSer), the cytotoxicity of CBL against K562 and COLO cells greatly exceeded the cytotoxicity of cultured adult peripheral blood lymphocytes. Culturing of CBL with rIL-2 and HuSer led to preferable generation of CD56+ cells. After 1 month in culture, the number and frequency of CD56+ cells had increased by more than 50 and nine times, respectively. The generation of CD56+ cells in CBL cultures may at least partially be explained by their comparatively strong expression of the IL-2 receptor (IL-2R) beta-chain (p75).
Subject(s)
Cytotoxicity, Immunologic/immunology , Fetal Blood/immunology , Interleukin-2/immunology , Killer Cells, Natural/immunology , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , CD56 Antigen , Cells, Cultured , Humans , Major Histocompatibility Complex/immunology , Recombinant Proteins/immunologyABSTRACT
The separate and combined effects of transforming growth factor-beta 1 (TGF-beta 1) and prostaglandin E2 on human natural killer (NK) activity were studied. Peripheral blood lymphocytes (PBL) and large granular lymphocytes (LGL, 70-90% purity) were used as effector cells and K562 as targets. Overnight incubation of the effector cells with TGF-beta 1 resulted in a significant inhibition of NK activity. TGF-beta 1 did not influence the expression of CD3, CD16, CD18 or CD56 antigens on PBL. Combination of TGF-beta 1 with indomethacin gave the same NK-suppressive effect as TGF-beta 1 alone, showing that the inhibition of NK activity by TGF-beta 1 is not due to an increase in PGE2 levels. TGF-beta did not influence cAMP level in PBL whereas PGE2 significantly increased it. On the other hand, TGF-beta 1 and PGE2 showed an additive inhibitory effect on NK activity. TGF-beta 1 did not reduce the binding of PBL and LGL to K562. PGE2 suppressed the binding and TGF-beta 1 did not influence this suppression. TGF-beta 1 also suppressed IL-2-induced activation of NK activity and increase of expression of the granule proteins granzyme A and perforin. PGE2 did not appear to affect granzyme A and perforin contents. The results indicate that TGF-beta 1 and PGE2 suppress NK activity by different mechanisms.
Subject(s)
Dinoprostone/pharmacology , Killer Cells, Natural/drug effects , Transforming Growth Factor beta/pharmacology , Cells, Cultured , Cyclic AMP/analysis , Granzymes , Humans , Interleukin-2/pharmacology , Killer Cells, Natural/chemistry , Killer Cells, Natural/immunology , Lymphocyte Activation/drug effects , Membrane Glycoproteins/analysis , Perforin , Pore Forming Cytotoxic Proteins , Serine Endopeptidases/analysisABSTRACT
The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II-IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II-IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyond that already available from staging. However, those stage II-IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.
Subject(s)
Lung Neoplasms/immunology , Lung Neoplasms/mortality , Aged , Cytotoxicity Tests, Immunologic , Cytotoxicity, Immunologic/immunology , Female , Humans , Killer Cells, Natural/immunology , Lung Neoplasms/pathology , Major Histocompatibility Complex/immunology , Male , Middle Aged , Neoplasm Staging , PrognosisSubject(s)
Lung Neoplasms/immunology , Chi-Square Distribution , Discriminant Analysis , Follow-Up Studies , Humans , Immunity, Cellular , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Middle Aged , Monitoring, Immunologic/statistics & numerical data , Neoplasm Staging , PrognosisABSTRACT
Under study were disturbances in the immune competent system in 245 patients with injuries of the chest and abdomen in dynamics of the early posttrauma period. Specific features of the disturbances were analyzed in the complicated and noncomplicated course of the trauma disease. The informative value and prognostic significance of certain indices are discussed as well as approaches to immune correction.
Subject(s)
Abdominal Injuries/complications , Immune System Diseases/etiology , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications , Wounds, Penetrating/complications , Abdominal Injuries/immunology , Abdominal Injuries/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Antibody Formation , Emergencies , Female , Humans , Immune System Diseases/immunology , Immune System Diseases/surgery , Immunity, Cellular , Male , Middle Aged , Prognosis , Thoracic Injuries/immunology , Thoracic Injuries/surgery , Wounds, Nonpenetrating/immunology , Wounds, Nonpenetrating/surgery , Wounds, Penetrating/immunology , Wounds, Penetrating/surgeryABSTRACT
The role of T-lymphocytes in natural cytotoxicity of splenocytes of C3HA mice after a single injection of 20-methylcholanthrene (20-MC) was investigated. A splenocyte suspension was treated with anti-T-cell serum and complement. This treatment was not shown to exert influence on the natural cytotoxicity of splenocytes within 1-13 days after injecting 20-MC.
Subject(s)
Antilymphocyte Serum/pharmacology , Cytotoxicity, Immunologic/drug effects , Methylcholanthrene/pharmacology , Mice, Inbred C3H/immunology , Spleen/drug effects , T-Lymphocytes/immunology , Animals , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Male , Mice , Spleen/cytology , Spleen/immunology , Time FactorsABSTRACT
The activity of natural killer (NK) cells was found to be significantly higher in females with various miscarriages than that in those with normal pregnancy. The highest NK cell activity was observed in females with interrupted pregnancy.
Subject(s)
Abortion, Habitual/immunology , Abortion, Threatened/immunology , Cytotoxicity, Immunologic/immunology , Killer Cells, Natural/immunology , Obstetric Labor, Premature/immunology , Abortion, Habitual/etiology , Abortion, Threatened/etiology , Adult , Female , Humans , Obstetric Labor, Premature/etiology , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, ThirdABSTRACT
Autotransfusion of sorbent blood was used in the complex treatment of 62 patients with gastric ulcer characterized by an unfavourable course. The course of autotransfusions favoured scarring of the gastric ulcer in 70.9% of patients, normalized the helper/suppressor relations of regulatory subpopulations of T-lymphocytes, normalized the indices of natural killer activity.
Subject(s)
Blood Transfusion, Autologous/methods , Hemoperfusion , Stomach Ulcer/therapy , Adult , Female , Humans , Immunity, Cellular/immunology , Leukocyte Count , Male , Middle Aged , Stomach Ulcer/immunology , Time Factors , Wound Healing/immunologyABSTRACT
A single injection of C3HA mice with various immunomodulators-ds-RNA, thymogene (TM) and cyclophosphamide (CY)--performed one day before transplantation of syngeneic hepatoma 22a cells led to a decrease in the tumor growth rate. The most prominent effect was found following the CY treatment. The NK cell activity estimated per spleen of mice treated with ds-RNA and TM was seen increased in comparison with the control mice not given the modulators. The rate of tumor growth was due probably to this fact. The protective effect of CY may be accounted for by a direct action of this agent on tumor cells.
Subject(s)
Adjuvants, Immunologic/pharmacology , Dipeptides , Killer Cells, Natural/drug effects , Liver Neoplasms, Experimental/immunology , Mice, Inbred C3H/immunology , Spleen/drug effects , Adjuvants, Immunologic/therapeutic use , Animals , Cyclophosphamide/pharmacology , Cyclophosphamide/therapeutic use , Cytotoxicity Tests, Immunologic , Drug Screening Assays, Antitumor , Killer Cells, Natural/immunology , Liver Neoplasms, Experimental/drug therapy , Male , Mice , Neoplasm Transplantation , Peptides/pharmacology , Peptides/therapeutic use , RNA, Double-Stranded/pharmacology , RNA, Double-Stranded/therapeutic use , Spleen/immunology , Time FactorsABSTRACT
The influence of macrophages on NK cell activity of C3HA mice on 1, 7 and 13 days after single i. m. injection of 20-methylcholanthren was investigated. It is shown that macrophages significantly stimulate this activity on the 13th day after carcinogen application.
Subject(s)
Killer Cells, Natural/immunology , Macrophages/immunology , Methylcholanthrene/toxicity , Neoplasms, Experimental/immunology , Spleen/immunology , Animals , Cell Adhesion/immunology , Cells, Cultured/immunology , Cytotoxicity Tests, Immunologic , Male , Mice , Mice, Inbred C3H , Neoplasms, Experimental/chemically induced , Time FactorsABSTRACT
Suspension of splenocytes of control C3HA mice and mice examined early after transplantation of mouse hepatoma 22a cells were fractionated by treatment with anti-T-sera (anti-thymocytes, antibrain and anti-suppressor-T-cells). This treatment leads to various changes in NK-activity due to elimination of different subpopulations of T-lymphocytes. This variability may be associated with the presence of two or more types of suppressor cells able to influence the NK-cells directly or by means of other immunocompetent cells.
Subject(s)
Antilymphocyte Serum/pharmacology , Killer Cells, Natural/drug effects , Liver Neoplasms, Experimental/immunology , Mice, Inbred C3H/immunology , Spleen/drug effects , T-Lymphocytes/immunology , Animals , Brain/immunology , Killer Cells, Natural/immunology , Male , Mice , Neoplasm Transplantation , Spleen/immunology , T-Lymphocytes, Regulatory/immunology , Time FactorsABSTRACT
The induction of tumor in C3HA mice after intramuscular injection with 20-methylcholanthrene is accompanied by a decrease in natural antitumor resistance. This conclusion is based on the observation of the decreased natural killer activity per total number of splenocytes, from the time of carcinogen application till the appearance of tumor nodes.
Subject(s)
Killer Cells, Natural/drug effects , Methylcholanthrene/toxicity , Mice, Inbred C3H/immunology , Neoplasms, Experimental/chemically induced , Spleen/drug effects , Animals , Cell Count/drug effects , Cytotoxicity, Immunologic/drug effects , Killer Cells, Natural/immunology , Male , Mice , Neoplasms, Experimental/immunology , Organ Size/drug effects , Spleen/immunology , Time FactorsABSTRACT
23 patients with pyo-septic diseases resistant to conservative therapy were treated by extracorporeal perfusion of xenospleen (EPXS). In 17 patients on EPXS a persistent detoxicating effect was achieved. 6 patients died. EPXS procedure was accompanied by a drop in medium-molecular lipid blood level and normalization of natural killer activity that was decreased considerably prior to EPXS. It is concluded that EPXS has a normalizing effect on the natural killer activity, which may be essential for resistance to infectious complications.
Subject(s)
Extracorporeal Circulation , Killer Cells, Natural/immunology , Lymphocytes/immunology , Sepsis/therapy , Spleen , Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Male , Middle Aged , Sepsis/immunology , SwineABSTRACT
Essential changes in the mononuclear glycocalix structure and function and a reduction of the blood natural cytotoxicity have been detected in children suffering from neurodermatitis. These shifts depended on the disease pattern and did not recover in clinical remission.
Subject(s)
Cytotoxicity, Immunologic/immunology , Leukocytes, Mononuclear/immunology , Neurodermatitis/immunology , Adolescent , Agglutination Tests , Child , Cytotoxicity Tests, Immunologic , Glycoproteins/immunology , Humans , Polysaccharides/immunology , Recurrence , Surface PropertiesABSTRACT
A decrease of the natural killer activity (NKA) of C3HA splenocytes after transplantation of hepatoma 22a cells was connected to some extent with the suppressor action of macrophages and T-lymphocytes. Elimination of the macrophages from the splenocyte suspension led to the increase of NKA. Addition of the macrophages to the nonadherent cells resulted in the NKA inhibition to the level of nonfractionated splenocytes. T-cell elimination with anti-T-serum and a complement led to the increase of NKA as compared to NKA of the nonfractionated splenocytes.
Subject(s)
Killer Cells, Natural/immunology , Liver Neoplasms, Experimental/immunology , Mice, Inbred C3H/immunology , Spleen/immunology , Animals , Cell Separation , Macrophages/immunology , Male , Mice , Neoplasm Transplantation , T-Lymphocytes/immunology , Time FactorsABSTRACT
A decreased natural killer activity was observed in patients with lung cancer as the disease progressed. Surgical intervention results in its elevation at the IIId stage, while the application of cytostatics or irradiation are efficient at the IIId and IInd stages. Pronounced sensibilization of the peripheral blood lymphocytes in cancer patients to normal and cancer tissue antigens was demonstrated with the help of the leukocyte adhesion inhibition test.
Subject(s)
Antigens, Neoplasm/immunology , Cytotoxicity, Immunologic , Killer Cells, Natural/immunology , Lung Neoplasms/immunology , Lung/immunology , Adult , Aged , Humans , Leukocyte Adherence Inhibition Test , Lung/pathology , Lung Neoplasms/pathology , Middle Aged , Neoplasm StagingABSTRACT
Decreased natural killer (NK) activity and its inverse correlation with the level of circulating immune complexes were shown. Lowered NK activity was found to be associated with unfavorable prognosis.