Enucleated target cells are susceptible to lymphocyte-mediated cytolysis.
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Animals↗
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Results for “Cytotoxicity Tests, Immunologic”
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Complement-dependent cytotoxicity of sera obtained from subacute sclerosing panencephalitis patients.
Human lymphoid cells (NC-37) persistently infected with either measles virus (Schwarz and TYCSA strains) or subacute sclerosing panencephalitis (SSPE) virus (Halle and Mantooth strains) were destroyed in the presence of complement by anti-measles sera as well as by sera from SSPE patients. The cytotoxic activity was demonstrated in both IgG and IgM fractions of measles convalescent sera, but only in IgG fraction of SSPE sera. Measles convalescent sera completely lost the cytotoxic activity to all the cell lines, when absorbed with any one of the cell lines, indicating that the viral surface antigens of these cell lines infected with measles or SSPE virus are identical. On the other hand, the cytotoxic activity of SSPE sera could not be readily absorbed with these cells. Thus, the affinity of SSPE sera for the viral surface antigens might be lower than that of measles convalescent sera.
Cell Line↗
Lymphocytotoxicity in mycosis fungoides.
The phenomenon of lymphocytotoxicity was demonstrated in 29 patients with mycosis fungoides, using a newly described epithelial cell culture system and an isotope marker, 125Iododeoxyuridine (125IUdR). Lymphocytotoxicity was demonstrated in patients in the generalized plaque and the erythroderma phases of the disease (P is less than or equal to 0.05). No significant lymphocytotoxicity was demonstrable in patients who were in the limited plaque (early) phase of the disease. It is hypothesized that this demonstration of lymphocytotoxicity in patients may be a manifestation of a delayed hypersensitivity response to an as yet unidentified antigen in the epidermis.
Cytotoxicity Tests, Immunologic↗
Natural cytotoxicity of human Fc gamma-receptor-positive T lymphocytes after surface modulation with immune complexes.
In humans T cells with surface receptors for the Fc fragment of IgG (Fc gamma receptors) (TG cells) are effector cells in antibody-dependent cellular cytotoxicity (ADCC) and in natural cytotoxicity. While Fc gamma receptors are required to mediate ADCC, their role in natural cytotoxicity is unknown. To investigate this question, Fc gamma receptors on effector cells were modulated by interaction with IgG immune complexes. As a consequence of this modulation, TG cells lost most of their ADCC activity but retained a significant part of their natural killer activity. Thus, these experiments demonstrate that the cytotoxic mechanisms exerted by the same cell population can be dissociated experimentally. Furthermore, they suggest that the net natural cytotoxicity of normal human lymphocytes in certain effector cell-target cell combinations is the result of distinct types of reaction.
Antibody-Dependent Cell Cytotoxicity↗
Immune effector cell activity in canines: failure to demonstrate genetic restriction in direct antiviral cytotoxicity.
Experiments were undertaken to establish whether the cytotoxic activity of canine immune effector cells against viral antigens was affected by the genotype of the target cell (genetic restriction). Puppies from three different breeds were infected with vaccinia virus, and the peripheral blood leukocytes were collected at various times for measurement of their cytotoxicity against autologous and heterologous vaccinia virus-infected and uninfected skin fibroblasts. In all cases cytotoxicity only occurred against virus-infected targets, and there was no consistent evidence of preferential killing of autologous targets. Several indirect approaches were used to demonstrate that direct, presumably T cell, cytotoxicity was being measured rather than antibody-dependent cell cytotoxicity. On the basis of the evidence from cross mixed-lymphocyte assays and cell-mediated lympholysis assays, the dogs were shown not be be identical with respect to their histocompatibility antigens. The significance of our findings to the phenomenon of genetic restriction as observed for mouse-derived immune effector cells is briefly discussed.
Animals↗
Effect of cell-mediated immune factors on the replication of an attenuated temperature-sensitive mutant of vaccinia virus.
Studies of the in vivo multiplication of an attenuated temperature-sensitive strain of vaccinia virus (ts2) indicated that temperature sensitivity alone could not account for the attenuation. Immunodepressive treatment of intracerebrally inoculated mice had a dramatic stimulatory effect on the multiplication of the attenuated strain and suggested that establishment of ts2 infection in the mice was hindered by host defense mechanisms mediated by cellular elements. Experiments carried out in vitro with the 51Cr release assay showed that cells infected with the ts2 mutant represented more susceptible targets to the cytotoxic action of immune spleen cells than cells infected with the parent vaccinia strain. Moreover, it appeared that ts2 replication, compared with wild-type replication in vitro, was more inhibited by the immune spleen cells. Although this work did not evaluate the role of specifically sensitized lymphocytes within the lesions, indirect evidence suggests that lymphocytes could cause a more effective halt in ts2 virus multiplication than in wild-type multiplication.
Animals↗
Cytotoxic antibody to cells infected with measles virus in serum and cerebrospinal fluid of multiple sclerosis and control patients.
Sera and cerebrospinal fluids (CSFs) from 66 patients selected from a larger sample of multiple sclerosis (MS) and control patients were studied for presence of complement-dependent cytotoxic (CT) antibody against baby hamster kidney cells infected with measles virus, strain Lec. The MS group contained 26 patients with clinically definite disease and 7 with probable MS. Seventeen of the 33 patients selected from the MS group had hemagglutination-inhibiting (HI) antibody to measles virus in their CSFs. Specimens from 33 control patients with other identifiable neurological disorders were matched according to the time of specimen sampling and with the age of the donors. Seven of the controls had HI CSF antibody. The serum CT geometric mean antibody titer of the MS group was approximately twofold higher than that of the control group. Forty-two percent of the MS group and 18% of the control group had CT antibody in the CSF. With the exception of the ratio of one control patient, the serum/CSF ratios of CT antibody from all patients were 128 or less. Nine CSFs (six MS and three control specimens) had CT antibody but no detectable HI antibody. Conversely, 12 CSFs (eight MS and four control specimens) had HI antibody but no detectable CT antibody. Five patients in the MS group with both kinds of CSF antibodies had reduced CT ratios but normal HI ratios. The results suggest that the two tests detect CSF antibodies reactive with different antigens. In this study, where less than half of the MS patients displayed CSF CT antibody, it is unlikely that such antibodies play an active role in the pathogenetic mechanism operative in the disease.
Antibodies, Viral↗
Lymphocytotoxicity test against rabbit hepatocytes in chronic liver diseases.
We have studied the cytotoxicity against rabbit liver cells of lymphocytes from the peripheral blood of 71 patients with various liver diseases. The group with chronic active hepatitis and three patients with acute alcoholic hepatitis showed significantly higher mean values of lymphocytotoxicity (P less than 0.001) compared with the other patients with chronic persistent hepatitis, post-necrotic fibrosis and cirrhosis. Wilson's disease, and prolonged viral hepatitis. The mean cytotoxicity of these last groups did not differ significantly from controls. In four out of six patients with chronic active hepatitis a significant decrease of lymphocytotoxicity was found after immunosuppressive therapy with oral prednisolone. A good correlation between the lymphocytotoxicity test and histological signs of activity suggests that a cell-mediated immune aggression is present in this disease.
Adolescent↗
Lymphocyte cytotoxicity in chronic active hepatitis: effect of therapy and correlations with clinical and histological changes.
A study of lymphocyte cytotoxicity for rabbit hepatocyte cultures in 15 patients with untreated chronic active hepatitis showed positive results in all cases, both HBsAg positive and negative. After immunosuppressive therapy cytotoxicity became negative and remained negative, in four of nine patients followed serially. In 51 patients established on therapy for periods from three months to 12 years, cytotoxicity was negative in 19 and all patients are currently alive. However, in the remaining 32 patients in whom cytotoxicity was positive there has been a 34% mortality. Cytotoxicity remained persistently positive in 12 of 15 patients followed serially, and persistently negative in seven of nine. Cytotoxicity showed a significant association with histological disease activity, especially the extent of piecemeal necrosis, but not with biochemical tests of liver function, immunoglobulins, or autoantibodies. The basis of this cytotoxicity test is an antibody dependent cell-mediated autoimmune reaction directed against a liver specific protein, and the results suggest that in some cases immunosuppressive therapy is followed by control of this reaction. It may be possible to stop therapy in these patients, but in those in whom the reaction continues, as shown by continuing cytotoxicity, the prognosis is not as good and the use of other drug schedules would seem worthy of trial.
Adult↗
Pulmonary cell-mediated cytotoxicity in hamsters with parainfluenza virus type 3 pneumonia.
A 51Cr-release cytotoxic assay in vitro was developed to permit definition of the role of local pulmonary cell-mediated immunity in the recovery phase of experimental parainfluenza virus type 3 pneumonia in the Syrian hamster. Cytotoxic effector cells were obtained by bronchalveolar lavage; virus-infected targets were syngeneic secondary hamster kidney cells. Maximal target-cell killing was mediated by lung lavage cells obtained one week after infection; the response waned rapidly thereafter. There was a close temporal correlation between the cytotoxic response and termination of virus replication in the lung. Cytotoxicity was virus specific and was restricted by a requirement for species identity between effector and target cells. Immune spleen cells mediated one-fourth the amount of 51Cr release effected by lung lavage cells, which suggests that cytotoxic effectors were concentrated in the lung. Although the identity of the cytotoxic effector cell was not established conclusively, the characteristics of the response suggested strongly that thymus-derived lymphocytes mediated lysis of target cells. Further work is required to determine the relative importance of this aspect of the host response during recovery from respiratory viral infection.
Animals↗
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↗
Immunobiology of primary intracranial tumors. Part 3: Microcytotoxicity assays of specific immune responses of brain tumor patients.
Fifty-six in vitro microcytotoxicity assays were conducted on 30 patients with intracranial tumors at various times during the postoperative course. Significant specific cellular cytotoxic responses were found in nine of 56 assays, humoral cytotoxic responses in nine of 54 assays, and host effector cell-dependent, antibody-dependent cytotoxic responses in four of 28 assays. Variables that might influence the occurrence of cytotoxicity were studied, and the relationship of these findings to other immune parameters was discussed.
Adolescent↗
Lymphocytotoxicity of chickens bearing Rous sarcomas.
A 51Cr uptake microcytotoxicity assay was used to determine the cytotoxicity of lymphocytes from chickens bearing Rous sarcomas. Differences in lymphocyte cytotoxicity among individual chickens were statistically significant. Lymphocytes from chickens regressing (or having regressed) their tumors were significantly more cytotoxic than lymphocytes from hosts with progressing tumors. Lymphocytes from chickens with progressing tumors tended to enhance tumor cell growth in vitro.
Animals↗
Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 1. Description of the reaction.
The presence of new antigens on hamster cells transformed by avian sarcoma viruses was investigated by in vitro cellular microcytotoxicity assays using spleen cells obtained from immunized hamsters as effector cells and monolayers of transformed cells as targets. The effect of a number of variables was studied especially the concentration of effector cells and of target cells. Probit analysis has been used to statistical interpretation of data. Spleen cells obtained from hamsters immunized with RSV transformed rat cells have allowed the demonstration of new antigens on transformed hamster cells. These antigens have been also detected, in certain conditions, using effector cells obtained from hamsters immunized with RSV transformed hamster cells.
Animals↗
Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 2. Sensitivity of different subclones.
The presence of new antigens on different subclones of hamster cells transformed by avian sarcoma viruses was investigated by an in vitro cellular microcytotoxicity assay. The RS 2/3 and RS 2/10 subclones derived from the RS 2 clone, transformed with a Schmidt-Ruppin strain of RSV were highly sensitive to the cytotoxic action of spleen effector cells obtainled from hamsters immunized with RSV-transformed rat cells. The RS 2/6 subclone was sensitive only when 1,000 target cells were seeded and the RS 2/7 subclone was not susceptible to the cytotoxic action of effector cells. The RB 12/1 subclone, derived from the clone RB 12, transformed with a Bryan strain of RSV was poorly sensitive. The comparison between the sensitivity to XC-sensitized spleen cells of the different subclones and their other known properties was discussed.
Animals↗
Cytotoxic T cell response to lymphocytic choriomeningitis virus. Properties of precursors of effector T cells, primary effector T cells and memory T cells in vitro and in vivo.
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Animals↗
[Studies on the spontaneous lymphocyte toxicity in colonic carcinoma].
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Colitis, Ulcerative↗