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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 451 records · Page 25Linked to original sources

Interferon suppresses antigen- and mitogen-induced leukocyte migration inhibition.

Although first recognized by its effect on virus-cell interactions, interferon (IFN) has a variety of other effects. It can affect cell proliferation, modify the immune response at several levels, enhance the cytotoxic action of lymphocytes, suppress antibody formation and inhibit the development of delayed-type hypersensitivity (DTH) reactions. Therefore we have now tested the effect of interferon on leukocyte migration inhibition (LMI), regarded as the counterpart in vitro of DTH in humans. We have found that IFN suppresses both mitogen-and antigen-induced LMI, acting directly on the granulocytes but also affecting the lymphokine production of the lymphocytes.

Antigens↗

Effect of interferon-alpha 1 from E. coli on some cell functions.

Interferon-alpha 1 from Escherichia coli transformed with a hybrid plasmid containing a human leukocyte complementary DNA insert, induces resistance to virus in appropriate target cells. It also shares the following properties with natural leukocyte interferon (IFN). (i) It enhances natural killing activity of human lymphocytes, (ii) it enhances antibody-dependent cell-mediated cytotoxicity, (iii) it suppresses antigen- and mitogen-induced leukocyte migration inhibition, (iv) it inhibits growth of IFN-sensitive Burkitt lymphoma cells. Since these activities are exhibited by a cloned protein species, they are due to IFN itself and not to other human proteins.

Antibody-Dependent Cell Cytotoxicity↗

Induction of the EBV cycle in B-lymphocyte-derived lines is accompanied by increased natural killer (NK) sensitivity and the expression of EBV-related antigen(s) detected by the ADCC reaction.

Human B-lymphocyte-derived lines were forced to enter the EBV-cycle by superinfection with the P3HR-1 substrain of EBV or sodium butyrate treatment. The induced cells were used as targets for natural killing (NK) and EBV-specific, antibody-dependent cellular cytotoxicity (ADCC). Two Burkitt lymphoma lines, Raji and Daudi, and one normal adult derived lymphoblastoid cell line, NAD-7, were comparable in their ADCC-sensitivity after induction, but only the Burkitt lymphoma-derived lines showed a major increase in NK-sensitivity. The superinfection-induced membrane change, responsible for both NK and ADCC sensitivity, is an early function of the viral cycle, correlated with the appearance of early antigens (EA). Indirect evidence indicates that the NK and ADCC target sites are different but this problem requires further investigation. Sodium butyrate induced an increased NK sensitivity and EBV-related ADCC sensitivity in the Burkitt lymphoma-derived P3HR-1 line. Lymphocyte effectors from different donors showed great differences in their NK and ADCC activity. Optimal ADCC could be demonstrated with effectors that were intermediate in their NK-activity.

Antibody-Dependent Cell Cytotoxicity↗

Surface immunoglobulins on Burkitt's lymphoma biopsy cells from 91 patients.

One hundred and fourteen biopsies from 91 cases of African Burkitt's lymphoma were examined by immunofluorescence methods for the presence of surface-associated mu, gamma, delta, kappa and lambda chains, as well as for the Fc region of gamma chains and for beta1C. Only 5% of the biopsies were surface-Ig-negative; 18% were negative for mu chains and 61% for gamma chains. Delta chain staining was absent, or borderline in a few tumors. Mu chains, gamma chains in a few highly reactive tumors and, in many cases, the predominant light chain seemed to be clonal markers. They gave no convincing evidence of more than one cell clone, either within single tumors or within syn- or metachronous tumors in one individual. Gamma chains in moderately stained tumors, Fc and beta1C correlated with each other and the first two reactivities decreased after incubation at low pH, indicating that their presence resulted from outside coating of the cells. The results indicated that one clone of B cells is involved in Burkitt's lymphoma in the large majority of cases. This clone is in a state of differentiation at which surface delta chains are not expressed. No prognostic information resulted from the analysis of the markers studied.

Biopsy↗

Role of alloantigens in natural killing. Allogeneic but not autologous tumor biopsy cells are sensitive for interferon-induced cytotoxicity of human blood lymphcoytes.

Blood lymphocytes of patients with solid tumors were assayed for cytotoxicity against autologous and allogeneic primary tumor cells. The lymphocytes killed autologous tumor cells in 7 of 25 cases (28%) and allogeneic tumor cells in 2 of 37 tests (5%). Lymphocytes from healthy donors were rarely cytotoxic for the biopsy cells, which indicates that these cells have low natural kill sensitivity. The autoreactivity that may reflect the immunological recognition of tumor cells was not altered by pretreatment of the effectors with interferon (IF). In contrast, killing of allogeneic tumor biopsy cells was induced by IF in approximately 50% of tests, with the lymphocytes of both the tumor patients and the healthy donors. The mechanism of the alloreactivity is most likely a consequence of IF-induced polyclonal activation of cytotoxic potential and the lymphocytes that are committed to recognize the alloantigens expressed on the particular target manifest the killing function. When the biopsy cells were explanted and kept in culture for 5-6 d, their susceptibility for the lymphocyte damage increased, and they were killed by the IF-treated cells also in autologous combinations. Whether this change in sensitivity is a result of qualitative or quantitative changes in antigen expression or of other changes in the properties of the cell membrane is unknown.

Adolescent↗

Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate.

Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK-sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.

Antigens, Viral↗

Activated T lymphocytes in infiltrates and draining lymph nodes of nasopharyngeal carcinoma.

Lymphocytes isolated from the tumors and draining lymph nodes of nasopharyngeal carcinoma (NPC) patients exhibit the following characteristics of immune activation: (1) stable E rosette formation, (2) natural attachment to various human cells, (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the NPC T cells attach in vitro to various cells they kill only EBV-genome-carrying targets. These findings suggest the occurrence of a local cellular immune response in NPC, possibly directed to EBV-determined antigens.

Cell Line↗

Treatment of Kaposi's sarcoma with vinblastine.

Fourteen patients with Kaposi's sarcoma (KSY were treated systemically with vinblastine sulfate in a low-dose regimen and compared with 23 patients reported in the medical literature. The therapeutic results in our series were excellent in terms of regression of cutaneous lesions. Vinblastine appears to be a drug that is well suited for the management of KS in an outpatient setting. Intravenous therapy may be supplemented with intralesional or intraarterial vinblastine.

Adult↗

Mycosis fungoides associated with florid sarcoid reactions.

We report a 59-year-old woman with disease manifestations diagnosed as mycosis fungoides (MF), as well as findings of sarcoidosis. The concurrence of these two disorders, both of which may be associated with basic immunopathogenic factors, has been reported. Histologically, the cutaneous findings of both non-caseating granulomas and an infiltrate compatible with MF in the same site leads to a discussion of granulomatous MF. Whether granulomatous MF simply represents sarcoidosis developing concomitantly with MF lymphoma or is, in fact, a distinct clinical and histologic type of MF is discussed. Reasons why granulomatous MF, like granulomators Hodgkin disease, might have a more favorable prognosis than the usual type of MF are considered.

Female↗

Somatic hybrids between a high NK-sensitive lymphoid (YACIR) and several low sensitive sarcoma or L-cell-derived mouse lines exhibit low sensitivity.

Mouse somatic cell hybrids between a high NK-sensitive lymphoma line (YACIR) and various sarcoma or L-cell-derived cell lines (all weakly sensitive) all exhibited low NK sensitivity. This was not due to a general resistance to cell-mediated lysis, since these mouse hybrids could be killed by in vitro-sensitized specific T cells. Alloantigens are usually codominantly expressed in somatic cell hybrids, whereas differentiation-related markers are usually suppressed. Because NK sensitivity was found to be suppressed, in contrast to the expression of alloantigens and tumor-associated antigens, we suggest that the target structure may be either a differentiation-related antigen or a differentiation-related "membrane property."

Animals↗

Decreased density in membrane localized macromolecules in cells enlarged after X-irradiation or polyploidization.

Cytophotometric measurements of DNA, dry mass (total proteins) and surface localized IgM and Ia were performed on individual cells of a Burkitt lymphoma derived cell line after X-irradiation and after polyploidization. Blockage of cell division was achieved with 250 r, and an arrest in G2 was found 48 hr after irradiation. The cells unable to divide increased in volume and total protein content. Cell enlargement was also achieved by polyploidization. The amount of surface localized IgM and Ia did not keep up pace with the increase in total proteins, thus their density decreased. This was reflected in decreased sensitivity of the enlarged cells to the cytotoxic effect of specific antisera.

Cell Line↗

Target selectivity of interferon-induced human killer lymphocytes related to their Fc receptor expression.

Human blood lymphocytes were fractionated on the basis of surface characteristics such as adherence to nylon wool and expression of erythrocyte (E) and Fc receptors. The various subsets were incubated with interferon for 3 hr. Two cell lines that differ in sensitivity to the natural killer effect, K562 and Daudi, were exposed to these lymphocytes (i.e., their sensitivity to interferon-activated killing was tested.) Cell line Daudi, with a low sensitivity to the natural killer effect, was also affected by interferon-activated killing. The efficiency of the nonadherent subsets, separated according to the expression E receptor, ranked similarly in natural killing (anti-K562) and interferon-activated killing (anti-K562 and anti-Daudi) in the following order: E receptor-negative cells, low-affinity E receptor-positive cells, and high-affinity E receptor-positive cells. Further separation on the basis of Fc receptor expression revealed a difference between the two targets. The Fc receptor-positive and -negative cells that did not express high-affinity E receptors killed K562 with similar efficiency whereas Daudi cells were more sensitive to the effect of cells devoid of Fc receptor. Results obtained with other targets suggested that T cell lines behave similarly to K562 and that the difference may be generally valid for T and B cell lines.

Animals↗