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At least 19 recordsLinked to original sources
PubMed1979

Leukocyte cytotoxicity in a persistent virus infection: presence of direct cytotoxicity but absence of antibody-dependent cellular cytotoxicity in horses infected with equine infectious anemia virus.

Antibody-dependent cellular cytotoxicity and direct cytotoxicity assays were performed with equine infectious anemia virus-infected target cells, equine leukocytes, and equine anti-equine infectious anemia virus antibody to determine whether these mechanisms play a role in controlling viral replication in equine infectious anemia. Direct cytotoxicity was observed by using peripheral blood mononuclear cells from 7 of 10 infected horses. Antibody-dependent cellular cytotoxicity was not observed. The antibody-dependent cellular cytotoxicity reaction in horses was then studied by using sheep erythrocytes and trinitrophenylated sheep erythrocytes as target cells. Lysis of these target cells was mediated by neutrophils, monocytes, and lymphocytes. The reaction was activated by antibody of the immunoglobulin G class but not by immunoglobulin G(T). Furthermore, immunoglobulin G(T) efficiently inhibited immunoglobulin G in this function.

Animals↗
PubMed1979

Human natural cell-mediated cytotoxicity against fetal fibroblasts. IV. Comparison of cytotoxic activity with antibody-dependent cell-mediated cytotoxicity.

The dependence of human natural killer (NK) cell activity on antibodies was investigated. Absorption of the culture medium with target cells, trypsinization of the effector cells followed by a brief recovery, and incubation of the effector cells in serum-free nutrient medium did not affect natural killer cell activity against fetal fibroblasts. No soluble mediator in the nutrient media of effector cell--fibroblast co-cultures could be demonstrated. It was therefore concluded that antibodies are not involved in the cytolytic activity of natural killer cells. However, competition data and the activity of isolated NK cells against antibody-coated target cells suggested overlapping between the effector cells mediating natural and antibody-dependent cell-mediated cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis. Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis.

The in vitro cytotoxic function and target cell specificity of peripheral blood lymphocytes from selected patients with primary biliary cirrhosis and hepatitis B surface antigen-negative chronic hepatitis were investigated using 51Cr-labeled human Chang and EL-4 mouse sarcoma cell targets in assays of spontaneous cell-mediated cytotoxicity (SCMC) and mitogen-induced cellular cytotoxicity (MICC). In addition, antibody-dependent cellular cytotoxicity (ADCC) against Chang cells was assessed. At an effector-to-target cell ration of 100:1, the mean SCMC against Chang cells was much less in patients with primary biliary cirrhosis than that in either the controls (P less than 0.001) or the patients with chronic hepatitis (P less than 0.005) whereas the value for patients with chronic hepatitis did not differ significantly from that of the controls. The mean SCMC against EL-4 mouse sarcoma cells was also less in patients with primary biliary cirrhosis than in controls (P less than 0.005) whereas the value for chronic hepatitis was not significantly different from that of the controls or patients with primary biliary cirrhosis. In contrast, MICC against both targets and ADCC against Chang cells were similar for each group. Comparison of SCMC and MICC against both target cells, measured simultaneously, showed similar cytotoxic potenital against both target cells for each group. Effector cells capable of mediating cytotoxicity in each assay were defined by testing the cytotoxic function of lymphocyte subpopulations isolated from two representative patients with each disease using techniques of immunoabsorbent affinity chromatography and Fc receptor binding to antigen-antibody complexes. In both primary biliary cirrhosis and chronic hepatitis SCMC and ADCC were mediated by a subpopulation of lymphocytes which lack surface immunoglobulin (sIg-) and bear Fc receptors (Fc+). In contrast, MICC was mediated by sIg- cells which lack Fc receptors. Lymphocytes bearing sIg- were not cytotoxic in any assay. These results establish a difference in cytotoxic function in primary biliary cirrhosis and chronic hepatitis by defining the presence of a defect in spontaneous cytotoxic function of sIg-, Fc+ lymphocytes against Chang cells in primary biliary cirrhosis.

Adult↗
PubMed1975

Subpopulations of multiparous rat lymph-node cells cytotoxic for rat tumour cells and capable of suppressing cytotoxicity in vitro.

Lymph-node cells (LNC) from multiparous pregnant rats were separated on columns prepared from nylon wool, and tested for cytotoxicity against target tumour cells. Reactivity of LNC towards hepatoma D23 and mammary carcinoma AAF57 was demonstrated in cell populations retained on the nylon wool, and not with cells eluted from the column. Although only 25% of the samples of unfractionated LNC were cytotoxic for tumour cells, retained cell fractions were cytotoxic in 11 out of 12 tests (p = less than 0.05). Similarly retained LNC were also cytotoxic for 15-day-old embryo cells but not for normal adult rat fibroblasts. Using multiparous rat serum it was shown that the reactivity of the retained LNC population could be abrogated in eight out of 11 tests (p = less than 0.05). The LNC population recovered from the nylon wool constituted 28 to 35% of the original LNC preparation, and consisted of 60-70% Ig-bearing cells together with a subpopulation of cells responding to soluble PHA. Separation of multiparous LNC on glass beads coated with rat Ig and then rabbit anti-rat Ig (in excess) also demonstrated the retained cell population to be cytotoxic against tumour cells. Approximately 17-20% of the original cell population was recovered from cells retained on the column, and consisted of an enriched Ig-bearing cell population (65-80% Ig-bearing cells) and LNC responsive to PHA. Carbonyl iron treatment of multiparous rat LNC was found to remove detectable cytotoxicity from multiparous rat LNC preparations. The cytotoxicity of multiparous rat LNC retained on nylon wool was also abolished following incubation with carbonyl iron. Definite conclusions as to the nature of the effector cell cannot be drawn from this test, since carbonyl iron treatment was found to remove not only phagocytic cells from LNC preparations but also a proportion of other cell populations including Ig-bearing lymphocytes... In addition to detecting a cytotoxic LNC population reactive towards tumour-associated embryonic antigens (retained fractions from nylon-wool column separation), a subpopulation of multiparous rat LNC was demonstrated in cell fractions eluted from the nylon wool which was shown to suppress the cytotoxicity of the retained multiparous LNC population. The exact nature of this subpopulation of LNC and the mechanism of action is at present not known.

Animals↗
PubMed1975

The cytotoxic activity of mouse T lymphocytes against allogeneic cytotoxic T cells.

Using a 51Cr cytotoxicity assay, the sensitivity of murine cytotoxic T cells to T cell mediated cytotoxicity has been tested. Two experimental approaches have been used. First, cytotoxic T-blast-lymphocytes (CTBL), enriched by the velocity sedimentation at 1 g were used both as cytotoxic effector cells and as 51Cr-labelled target cells. It was found that murine CTBL are capable to lyse directly and specifically allogeneic CTBL within 200 minutes. The second approach used was to incubate CTBL together with CTBL, the cytotoxic activity of which was directed against the transplantation antigens of the added allogeneic CTBL population. After 10 hours, the residual cytotoxic activity was tested. Again it was found that CTBL were capable of functionally inactivating allogeneic CTBL. Therefore the results obtained are incompatible with the concept that target cell lysis by cytotoxic T lymphocytes is mediated by a non specific "lymphotoxin", secreted by activated T cells after the antigen-recognition phase in the confined space between T cells and target cells.

Animals↗
PubMed1978

Cell types involved in cytotoxicity induced by heated cells and inhibition of this cytotoxicity by anti-human B cell sera.

We have studied the induction of cytotoxic activity in human peripheral blood lymphocytes by heated allogeneic cells. By separating T and B cells from the responder and stimulator cell populations we found that cytotoxic cells are generated in responder T cell populations by both T and the B stimulator cells. Rabbit antisera to a membrane glycoprotein complex (33,000 and 27,000 m.w. by SDS-gel electrophoresis) isolated from a human B cell line were utilized to explore further the nature of the effector cells in this type of cytotoxicity. This antiserum, present during the 6-day-culture period, blocked generation of cytotoxic effector cells. Depletion of cells bearing the B cell antigen from the responder cell population by anti-B cell serum and complement (C) eliminated cytotoxicity. Furthermore, heated cell-induced cytotoxicity was blocked by simply pretreating the responder or the stimulator cell populations with anti-B cell serum in the absence of C. Apparently the human lymphocyte that functions as the effector cell in heated cell-induced cytotoxicity bears the Ia-like antigen that might be important in triggering this type of cytotoxicity.

Antilymphocyte Serum↗
PubMed1979

Direct cytotoxicity against chicken erythrocytes in mice. II. Nature of immunoglobulin on cytotoxic T lymphocytes.

Direct cytotoxicity raised at an early interval after immunization with chicken erythrocytes (CRBC) has been ascribed to O-positive, immunoglobulin (Ig)-bearing lymphocytes. Cytotoxicity of such effector cells was not affected by trypsinization. Cytotoxity was reduced by the treatment of effector cells with anti-IgG serum and complement or by the addition of anti-IgG serum to culture medium for cytotoxicity test. When the effector cells were treated with trypsin before cytotoxicity test, such procedures with anti-IgG serum did not affect their cytotoxicity. Ig molecules on cytotoxic T lympohcytes may not be an essential element for antigen recognition. This explanation may be supported by the fact that cytotoxicity against CRBC could be raised in 600 rad irradiation, thymus-cell transferred mice in the absence of antibody production.

Animals↗
PubMed1979

Augmentation of cell-mediated cytotoxicity to a rat lymphoma. II. Characterization of the non-T cytotoxic cells stimulated in vivo by tumour cells as natural killer cells.

A variety of tumours injected into rats were found to rapidly stimulate cytotoxicity which was similar to naturally-occurring cytotoxicity of normal rats. Cytotoxic cells from the spleen and peritoneal cavity closely resembled NK cells in their lytic specificity and cell-surface characteristics. Thus, although cytotoxicity could be stimulated "non-specifically" with tumours which were resistant to lysis in vitro by NK cells, the cytotoxic cells exhibited patterns of specificity against a panel of target cells in direct lysis or competitive inhibition assays which were similar to those of NK cells from normal rats. These cells also closely resembled NK cells in being largely non-adherent, non-T cells, and in exhibiting a similar heterogeneity in the expression of Fc receptors. Thus, cytotoxicity which was augmented shortly after tumour inoculation appeared to be attributable to NK cells. However, whilst the majority of NK cells from normal or tumour-inoculated rats shared these properties, significant heterogeneity was observed. Minor populations of cytotoxic cells were adherent, were lysed by a heterologous anti-T-cell antiserum and complement and did not express an Fc receptor, although it was not determined whether the same subpopulation possessed all three characteristics.

Animals↗
PubMed1979

Deficiency of antibody-dependent cellular cytotoxicity and mitogen-induced cellular cytotoxicity effector cell function in patients with acute myelogenous leukemia in remission.

Patients with acute myelogenous leukemia in remission have pronounced deficiency in antibody-dependent cellular cytotoxicity (ADCC) and mitogen-induced cellular cytotoxicity. The deficiency in ADCC was partly explained by reduction in the number of circulating effector cells (Fc receptor-bearing cells) demonstrable at a time when white blood cell and platelet counts were normal. These cytotoxic functions, as well as the circulating numbers of T-cells and Fc receptor-bearing cells were further decreased by the administration of monthly cycles of combination chemotherapy with 1-beta-D-arabinofuranosylcytosine and 6-thioguanine. Following each cycle of chemotherapy, progressive recovery of these functions occurs during the third and fourth weeks with occasional increases above base line in patients in whom chemotherapy is withheld for longer than five weeks. In selected patients recovery of one cytotoxic function preceded the other, indicating that these functions are mediated by different effector cells. Administration of a single dose of daunomycin i.v. had no effect in either of these cytotoxic functions or in the circulating numbers of lymphocytes. The decrease in ADCC effector cell function induced by phase cycle-specific agents correlated with the level of reactivity exhibited by patients after achieving bone marrow and clinical remission. Patients showing low levels of reactivity postremission experienced highest degree of depression. In two patients, complete abrogation of ADCC effector function was demonstrated with minimal recovery even six weeks after stopping chemotherapy. These findings indicate that effector cells in ADCC and mitogen-induced cellular cytotoxicity are highly susceptible to phase cycle-specific agents, and their recovery takes longer that of other lymphoid and nonlymphoid populations.

Adult↗
PubMed1979

Augmentation of cell-mediated cytotoxicity to a rat lymphoma. I. Stimulation of non-T-cell cytotoxicity in vivo by tumour cells.

The injection of a syngeneic Gross-virus-induced lymphoma into W/Fu rats induced peaks of cytotoxicity in the spleen attributable to non-T cells and T cells 3 and 10 days later, respectively. The conditions required for augmenting the cytotoxicity of the non-T cells in various lymphoid compartments (shown elsewhere to closely resemble NK cells) were analysed using the ip and iv routes of inoculation and a variety of tumour cells including those normally susceptible or resistant to lysis by NK cells in vitro. Using an ip inoculation of W/FuG-1 cells (a tumour susceptible to lysis by NK cells), a short-lived, 3-fold increase in cytotoxicity was observed in the spleen at day 3 and a 5-fold increase in the PEC at day 5. Cytotoxicity in other lymphoid organs remained unchanged. Tumours resistant to lysis by NK cells also stimulated cytotoxicity in the spleen or PEC, although the effect depended on the dose and route of inoculation used, and depression of cytotoxicity was observed under some conditions.

AKR murine leukemia virus↗
PubMed1977

Generation of cytotoxic T lymphocytes during coxsackievirus tb-3 infection. II. Characterization of effector cells and demonstration cytotoxicity against viral-infected myofibers1.

This report describes studies characterizing the virus-specific cytotoxic effector cells which are present in the spleens of mice 7 days after infection with Coxsackievirus B-3. An in vitro 51Cr assay employing eyngeneic virus-infected neonatal fibroblasts was used to measure cytotoxic activity. Treatment of immune cells with (anti-thy-1.2) and complement abolished dtheir cytotoxic activity, but no reduction occurred when B cells were removed by incubation with anti-Ig and complement or macrophages eliminated by adherence depletion. The findings therefore imply that the cytotoxic reaction was mediated by sensitized T cells and that B cells and macrophages did not play an important role. Reciprocal assays performed with BALB/c and CBA/J cells showed that Coxsackievirus-immune spleen cells lysed infected syngeneic targets but not allogeneic targets, providing further evidence that cytotoxicity was mediated by effector T cells. In addition and in vitro assay system employing neonatal myocardial cells was developed and used to demonstrate that Coxsackievirus-infected myofibers were susceptible to destruction by immune spleen cells. The evidence suggests that mice infected with Coxsackie B viruses are able to mount a cell-mediated immune response with production of cytotoxic T cells which have the capacity to damage tissues infected with these agents.

Animals↗
PubMed1979

Direct cytotoxicity against chicken erythrocytes in mice. III. Degrees of radiosensitivity and cross-reactivity of cytotoxicity, delayed hypersensitivity and antibody production.

Exposure to 600 rad of X-irradiation 3 h after primary immunization with chicken erythrocytes (CRBC) abolished the production of antibodies and the generation of killer T cells, but scarcely affected the induction of delayed footpad reactions. Exposure to irradiation 3 h after secondary immunization reduced only slightly the generation of killer T cells and reduced slightly or substantially the production of antibodies. Delayed reactions persisted for long periods after elicitation in irradiated, boosted mice. Cross-reactivity between CRBC and quail erythrocytes (QRBC) was very weak with respect to the cytotoxicity, antibody and delayed reaction raised after primary immunization. Those raised after secondary immunization with the homologous antigen showed some degrees of cross-reactivity to another antigen. The booster with QRBC in CRBC-primed mice augmented the response to CRBC with respsect to the induction of cytotoxicity and delayed footpad reaction, but only weakly affected the response with respect to the production of antibody. Therefore, effector cells of cytotoxicity and delayed footpad reaction showed greater degrees of cross-reactivity than antibody-producing cells during an anamnestic response. The cross-reactive response raised after secondary immunization was radioresistant with respect to cytotoxicity and delayed footpad reaction but radiosensitive with respect to antibody production. Cytoxicity to immunizing antigen was inhibited by the unlabelled homologous antigen. Cytotoxicity to a cross-reacting antigen was inhibited by the same cross-reacting antigen and also by an immunizing antigen. There may exist heterogeneous populations of cytotoxic lymphocytes with different abilities to recognize antigens.

Animals↗
PubMed1977

Direct cytotoxicity against chicken erythrocytes in mice. I. Fundamental nature of T cell-mediated cytotoxicity.

Immune responses were examined after immunization with chicken erythrocytes (CRBC) in mice. Cytotoxicity of spleen cells was assessed by the release of 51Cr from labelled target cells. (1) At early stages (day 4-7) after primary intraperitoneal immunization, direct cytotoxicity of spleen cells was raised efficiently in C57BL/6 and AKR mice, but not in C3H/He, SL and DDD mice. Delayed hypersensitivity and antibody production were raised to almost the same extent in all the strains at such periods. (2) Effector cells in direct cytotoxicity were theta-positive and IgG-positive, and glass-nonadherent and Nylon wool column-adherent. Effector cells in antibody-dependent cell-mediated cytotoxicity in the presence of antibody to CRBC were eliminated by treatment with anti-IgG serum, but not by treatment with anti-theta serum. (3) Cytotoxicity and antibody production were raised efficiently after intraperitoneal or intravenous immunization, but not after footpad immunization. On the other hand, delayed hypersensitivity developed most efficiently after footpad immunization.

Animals↗
PubMed1979

Modulation of natural cytotoxicity by alloantibodies. I. Alloantisera enhancement of cytotoxicity of mouse spleen cells toward a human myeloid cell line.

Natural killer activity of spleen cells obtained from different strains of mice against the human myeloid leukemia cell line, K562, and two mouse cell lines P815 and L1210 was measured by using the 4-hr chromium release assay. The level of cytotoxic activity of spleen cells against the K562 target was usually less than 4% lysis. However, treatment of the spleen cells with a specific anti-H-2 antiserum resulted in a dose-dependent augmentation of the degree of lysis of K562 cells. The augmentation of cytotoxic activity could be obtained by pretreatment of the spleen cells with antisera or by directly adding the antisera to the cytotox-incubation medium. Anti-thy-1 and anti-immunoglobulin antisera had no enhancing effect under similar conditions. The specific alloantisera-treated spleen cells did not show any increase in cytotoxicity against P815 and L1210 target cells. Spleen cells responsible for the alloantiserum-mediated augmentation of cytotoxicity against K562 cells appear to be different from T or B cells as indicated by their resistance to anti-thy-1 and complement treatment and lack of adherence to nylon wool columns.

Animals↗
PubMed1978

Human monocyte cytotoxicity to tumor cells. I. Antibody-dependent cytotoxicity.

Recent investigations examining mononuclear cell antibody-dependent cell-mediated cytotoxicity against tumor cell lines suggest that K lymphocytes and not monocytes are active in this cytotoxic reaction. We have found, however, that in an allogeneic assay system, human monocyte monolayers as well as lymphocytes mediate substantial lysis of 51Cr-labeled antibody-coated CEM lymphoblast tumor cells. This cytotoxicity is temperature-dependent and rapid, with most 51Cr release occurring in the first 4 hr of co-incubation. Interaction between target cell-bound antibody and the monocyte Fc receptor is necessary as demonstrated by the marked fall in antibody-dependent cell-mediated cytotoxicity (ADCC) produced by staphylococcal protein A, high concentrations of nonspecific immunoglobulin, and dilution of the target cell antiserum. Morphologic and functional characteristics of the monocyte-monolayer preparations establish their relative purity (greater than 95%) and indicate that monocytes and not contaminating lymphocytes are responsible for tumor cell lysis. Furthermore, preincubation of monocyte and lymphocyte preparations with latex particles or low concentrations of immunoglobulin distinguished monocyte from lymphocyte ADCC. Thus, normal human monocytes have the capacity to carry out antibody-dependent cytotoxicity against nucleated malignant target cells.

Antibody-Dependent Cell Cytotoxicity↗