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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 415 records · Page 23Linked to original sources
PubMed1982

Breast cancer skin test antigens of increased sensitivity prepared from vesicular stomatitis virus-infected tumor cells.

Crude membrane (CM) extracts were prepared from five cultured breast tumor lines (MDA-MB-157, MDA-MB-231, ZR75-1, HS0578T, and MCF-7) which had been infected with vesicular stomatitis virus (VSV) to augment their antigenicity. In skin test trials, CM extracts of uninfected MCF-7 cells elicited positive response in 0 of 13 (0%) tests in breast cancer patients, while VSV-MCF-7 elicited positive responses in 11 of the same 13 patients (84.6%). CM extracts of VSV-ZR75-1 and VSV-MCF-7 elicited greater delayed hypersensitivity responses (mm induration at 48 hr) in breast cancer patients than in patients with lung carcinoma or melanoma. Although the sensitivity of VSV-ZR75-1 was too low (ten of 28, or 35.7% of tests positive) to be useful as a skin test antigen, VSV-MCF-7 elicited positive responses in 30 of 38 (78.9%) tests in breast cancer patients, as compared to two of 15 (13.3%) and two of 13 (15.4%) of tests in patients with lung carcinoma and melanoma, respectively. The "virus-augmented" CM extract of cultured MCF-7 cells exhibited markedly greater sensitivity as compared to control MCF-7 extracts (P less than .005), with a high degree of specificity for breast cancer patients as compared to patients with the other neoplasms (P less than .00001). The results of skin testing with VSV-MCF-7 CM extracts demonstrated antigenic cross-reactivity with a large number of breast cancer patients, a finding of great importance for any potential immunotherapy and/or immunodiagnosis.

Adult↗
PubMed1982

Specificity of auto-tumor cytotoxicity exerted by fresh, activated and propagated human T lymphocytes.

The specificity of auto-tumor cytotoxicity exerted by patients' T lymphocytes was investigated. Lymphocytes, both activated and non-activated, were used as effectors against freshly separated tumor cells. Activation was achieved by treatment with interferon (Hu-IFN-alphas), stimulation with PHA, co-cultivation with autologous tumor biopsy cells (ATS) and allogeneic lymphocytes (MLC). Of these activation systems, ATS was the most efficient in generating auto-tumor cytotoxicity. In some cases the lymphocytes activated in MLC or treated with PHA also damaged autologous tumor cells, but IFN-pretreatment of the lymphocytes had no such effect. When the ATS- or MLC-activated lymphocytes were propagated with conditioned medium known to contain Interleukin-2, their lytic potential against autologous tumors was maintained. In addition to autologous tumor biopsy cells, the effector populations were also confronted with other targets such as Con A blasts and allogeneic tumor biopsy cells. The latter were lysed by the lymphocytes activated in MLC, but not by the ATS cultures. Thus, on the population level, the ATS was specific for the autologous tumor cells. Cold target competition tests suggested that in the MLC-s the autologous tumor cells were killed by a distinct set of lymphocytes because allogeneic cells (tumor cells or the stimulator lymphocytes), even if killed by the same effector populations, did not compete. Thus, in these cultures the auto-tumor specificity of the lysis was on the level of the effector subset. Therefore, it is likely that, independently of the mode of activation, the auto-tumor lysis is the function of lymphocytes which recognize tumor- or organ-specific antigens on the target cells.

Carcinoma↗
PubMed1982

Lysis of tumor biopsy cells by autologous T lymphocytes activated in mixed cultures and propagated with T cell growth factor.

Blood lymphocytes from tumor patients were cocultivated with allogeneic lymphocytes (MLC) or autologous tumor cells (ATS), and their cytotoxicity was characterized. The main objective of the study was the lysis of autologous tumor biopsy cells by such effectors. Lymphocytes of patients activated in MLC lysed allogeneic third-party cells and in some cases also lysed autologous tumor cells. Allogeneic but not autologous PHA blasts were also damaged by these effectors. The cytotoxic potential of MLC-activated lymphocytes from healthy donors was similar; allogeneic tumors and phytohemagglutinin (PHA) blasts but not autologous PHA blasts were lysed. The cytotoxicity of lymphocytes activated in ATS were specific for the stimulator because they acted only on the autologous tumor cells. Allogeneic tumors and autologous and allogeneic PHA blasts were not lysed. The pattern of cytotoxicity with regard to this target panel was maintained when the MLC or ATS cultures were further propagated with TCGF. Results obtained in cold target competition assays suggested (a) activated lymphocyte lyse the third party tumor targets because of alloantigen recognition; (b) in MLC several different sets of alloreactive cytotoxic lymphocytes are present simultaneously; and (c) the alloreactive cells are different than those that act on the autologous tumor cells. Thus, the lysis of allogeneic tumor cells by lymphocytes of the patient is not due to recognition of cross-reacting tumor-related antigens, and the autotumor cytotoxicity of the patients' MLC-activated lymphocytes if performed by specifically reacting cells.

Binding, Competitive↗
PubMed1982

Human T-cell cultures with selective autotumor reactivity.

T-cell cultures derived from the blood of 14 patients with solid tumors were propagated with T-cell growth factor (TCGF). The cultures were initiated from lymphocytes exposed to autologous tumor-biopsy cells. TCGF was added either immediately or 3-10 days later. In the former culture type the cell yield on day 7 was considerably higher. The cytotoxic potential of the cultured cells was assayed on two occasions, between days 7 and 10 and between weeks 5 and 8. Cells of all but two cultures had the potential to lyse autologous tumor-biopsy cells. On the population level, cytotoxicity was specific for autologous tumor in those cultures that were driven to growth with TCGF after the 3rd day. These lymphocytes did not lyse allogeneic tumor-biopsy cells. In contrast, all five cultures initiated in the presence of TCGF exhibited a broader cytotoxic potential, i.e., in addition to the stimulator autologous-tumor cells, they also lysed other targets. Another difference between the two culture types was their behavior toward K562. Tested on the 7th day they all lysed K562; however, this function declined in strength or disappeared later in the cultures exposed to TCGF after the 3rd day. Reexposure of the lymphocytes to autologous tumor-biopsy cells after 2 weeks of culture period, but not on the 7th day, induced DNA synthesis. This secondary response was specific inasmuch as allogeneic tumor cells had little or no effect. One of the autotumor restimulated cultures was tested for cytotoxic potential. It increased against the autologous but not against other tumors or K562 cells.

Cytotoxicity, Immunologic↗
PubMed1982

Alloreactive cytotoxicity of interferon-triggered human lymphocytes detected with tumor biopsy targets.

Interferon activation of lymphocytes produces lytic potential against allogeneic but not against autologous biopsy-derived tumor cells. This effect was seen when targets isolated from solid tumors were used directly without cultivation in vitro. The hypothesis that the lytic effect was due to activation of alloreactive cells was tested in the cold target competition assay. The results substantiated our assumption because they showed that in a given lymphocyte population separate sets act on allogeneic tumor cells derived from different individuals. In addition PHA blasts from the target-cell donor but not from unrelated individuals also inhibited the lysis. The system we use is operationally an NK assay in which antigen (MHC)-recognizing lymphocytes seem to function. Since antigen recognition is a property of the T subset, the conceptual dualism in the classification of NK and CTL effects should be modified.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Role of H-2 antigens in the host response to methylcholanthrene-induced tumors.

H-2 loss variant sublines of a sarcoma (M-AS), induced by methylcholanthrene in an (A x A.SW)F1 mouse, were used to study the role of the MHC products in the recognition of MC-TSTA. The two reciprocal variant sublines (M-A and M-S) were found to express the TSTA of the original tumor as shown by cross-reactions in graft rejection experiments performed in (A x A.SW)F1 mice. In the A/Sn and A.SW mice the presence of the reciprocal parental H-2 antigens on the immunizing cells decreased the response against the tumor antigens. An admixture of lymphocytes derived from hyperimmune mice inhibited the outgrowth of the tumor cells. The growth inhibition was mediated by T cells and was H-2 restricted. Cells derived from hyperimmune immunization but had no effect on the reciprocal variant subline.

Animals↗
PubMed1982

Human T cell growth factor (TCGF) produced by repeated stimulation of non-adherent human lymphocytes.

T cell growth factor (TCGF) has become a valuable means of maintaining T lymphocytes in long-term culture and of studying T cell function. Numerous problems have been met in the production of TCGF of consistently good quality and in the maintenance of human T cell lines over long periods. We have investigated optimal conditions for TCGF production, and simplified assay systems for TCGF activity. The best TCGF production was obtained by short-term treatment with high concentrations of phytohemagglutinin (PHA). The TCGF producing lymphocytes could be re-used for TCGF production up to 1 month after the first treatment course. Human cultured T cell lines, fresh lymphocytes, short-term PHA stimulated lymphocytes and cultured marmoset T lymphocyte lines were all used for assay of TCGF. We recommend PHA stimulation of human lymphocytes for this assay on a routine basis, comparing results with a standard TCGF batch and calculating a growth index. Adherent cells impair TCGF production. Optimal TCGF production was seen when lymphocyte preparations without adherent cells from different donors were used.

Animals↗
PubMed1982

Natural killer activity of human blood lymphocytes.

Natural killer (NK) activity is an operational designation. It implies the in vitro cytotoxicities registered in short-term tests exerted by lymphocytes derived from donors with no known immunization history against the particular target. The strength of the effect exerted by unmanipulated blood lymphocytes shows an individual variation. Short-term in vitro treatment with interferon elevates the lytic potential of lymphocytes. Owing to the heterogeneity of the cytotoxic blood lymphocytes with regard of cell surface properties it is not possible to separate all active cells and inactive cells in clean populations. A considerable enrichment of active cells can be achieved if nylon wool non-adherent, large, granular Fc gamma receptor positive SRBC receptor negative--or low-avidity SRBC receptor positive--OKM1-reactive cells are separated. Negative cells are concentrated in the Fc receptor and OKM1-negative high-avidity SRBC receptor positive high cell density subset. The activity of lymphocytes in the former category is potentiated by interferon and the latter acquire the lytic function if PHA is added to the assay system. Freshly separated, non-cultured tumor cells are not or weakly sensitive to the effect of unmanipulated lymphocytes. However, when the lymphocytes are treated with interferon prior to the assay a lytic potential can be induced even against these in allogeneic effector target combinations. Cytotoxic cells which acquired the function after in vivo and/or in vitro immunization are designated as 'cytotoxic T-lymphocytes' (CTL), and were shown to act on the basis of antigen recognition. The expression of known T-markers on at least a fraction of the active cells and the recognition of alloantigens in NK systems suggest that the distinction between CTL and NK cells is not as sharp as initially suggested.

Animals↗
PubMed1982

IFN-alpha-induced modulations of the events in human mixed lymphocyte cultures.

Autologous mixed lymphocyte cultures (AMC) with T-enriched subset of human blood lymphocytes as responders and B-cells or plastic adherent cells as stimulators and allogeneic mixed lymphocyte cultures (MLC) were assayed for blastogenesis and generation of cytotoxic potential. The activated cells lyzed K562 and Daudi, autologous and allogeneic PHA-blasts. The AMC population affected the autologous and allogeneic blasts at a similar strength and there was no indication for selective effects. B-Blasts induced with Staphylococcus aureus were not lyzed. The MLC populations had a stimulation-specific cytotoxic component. This was revealed by the stronger effect against the stimulator PHA-blasts and by the lysis of the stimulator B-blasts. Short-time interferon (IFN) treatment prior to the lytic assay enhanced the anti-Daudi and anti-K562 lytic activity of the AMC and MLC populations. With AMC the lytic efficiency against the autologous and allogeneic PHA-blasts were not changed while with MLC they were also elevated. This increase was confined to the non-specific component of the cytoxicity. The proliferation of lymphocytes was suppressed when interferon was added at the initiation of the mixed cultures. On a per-cell basis the cytotoxic potential of these cultures were stronger. In the MLC the stimulation-specific component increased more substantially than the effect against the non-specific targets. It is possible that the IFN-induced modification of the culture conditions such as suppression of the initial proliferation favored the growth of the specific clone. Re-exposure of these cells to another dose of interferon prior to the lytic assay had no effect on the lytic potential.

Cell Line↗