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Y Segev

Publications and source records attributed to Y Segev.

45 records · Page 3Linked to original sources
PubMed1993

Thymic humoral factor, THF-gamma 2, enhances immunotherapy of murine cytomegalovirus (MCMV) infection by both CD4+ and CD8+ immune T cells.

Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. The contribution of the different spleen cell subsets in conferring curative immunocytotherapy to fatally MCMV-infected immunosuppressed mice was assessed using adoptive immunotherapy. It was found that the efficacy of passively transferred immune spleen cells is dose dependent and that the therapeutic effect can be enhanced considerably by treating donor mice with thymic humoral factor (THF-gamma 2). Polymerase chain reaction (PCR) of the donor spleen population was negative, indicating that no MCMV-DNA was transferred with the immune cells. Analysis of the donor mice after THF-gamma 2 treatment showed increased levels of CMV-neutralizing antibodies, while enhancement of natural killer (NK) activity was transient and lasted only during the early phase of the infection. FACS analysis demonstrated that treatment with THF-gamma 2 restored the size of both cell subsets CD4+ and CD8+ that were decreased following MCMV infection. It is shown that both CD4+ and CD8+ T-cell subsets participate in controlling the development of the fatal disease in MCMV-infected immunosuppressed recipients. It is suggested that the enhancement of the immunocompetence of both populations of spleen cells from treated donors is mediated in part by the restoration of Interleukin-2 (IL-2) production by THF-gamma 2.

Animals↗
PubMed1992

Persistent measles virus infection enhances major histocompatibility complex class I expression and immunogenicity of murine neuroblastoma cells.

The effect of persistent measles virus infection on the expression of major histocompatibility complex (MHC) class I antigens was studied. Mouse neuroblastoma cells C1300, clone NS20Y, were persistently infected with the Edmonston strain of measles virus. The persistently infected cell line, NS20Y/MS, expressed augmented levels of both H-2Kk and H-2Dd MHC class I glycoproteins. Activation of two interferon(IFN)-induced enzymes, known to be part of the IFN system: (2'-5')oligoadenylate synthetase and double-stranded-RNA-activated protein kinase, was detected. Measles-virus-infected cells elicited cytotoxic T lymphocytes that recognized and lysed virus-infected and uninfected neuroblastoma cells in an H-2-restricted fashion. Furthermore, immunization of mice with persistently infected cells conferred resistance to tumor growth after challenge with the highly malignant NS20Y cells. The rationale for using measles virus for immunotherapy is that most patients develop lifelong immunity after recovery or vaccination from this infection. Patients developing cancer are likely to have memory cells. A secondary response induced by measles-virus-infected cells may therefore induce an efficient immune response against non-infected tumour cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells.

Application of neutralizing anti-hemagglutinin antibodies to mouse neuroblastoma cells (NS20Y/MS) persistently infected with measles virus (MV) leads to a significant reduction of viral structural proteins within 6 days. While the transcriptional gradient for MV-specific mRNAs remained unaffected upon antibody treatment, the total amount of MV-specific transcripts dropped by 80% after 24 h. The expression of genomic RNA was affected similarly, with slightly slower time kinetics. Both transcription and expression of the viral structural proteins could be completely reactivated when viral antibodies were removed from the tissue culture. The same findings could be obtained in rat glioma cells persistently infected with subacute sclerosing panencephalitis virus (C6/SSPE) but not in cells of nonneural origin. The data indicate that antibody-induced antigenic modulation affects the early stages of viral transcription within a few hours after the addition of antibodies and leads to an almost complete repression of viral gene expression in cells of neural origin.

Animals↗
PubMed1990

Natural killer (NK) cell response after vaccination of volunteers with killed influenza vaccine.

Many experiments have shown convincingly that natural killer (NK) cell activity against viral infections is an important early defence mechanism in mice. Since the NK response occurs soon after infection, often long before clinical signs of disease become manifest, it has been difficult to design studies to monitor accurately NK cell kinetics following infection, without actually administering pathogens to volunteers. There is therefore little data pertaining to the role of NK cells in humans. Nevertheless, a number of studies have shown elevated NK activity in response to herpes simplex and influenza virus infections in humans. Our study was designed to show that NK activity could be provoked in humans by exposure to viral particles without actual live viral infection. The development of NK cell response in the peripheral blood of volunteers shortly after vaccination with killed influenza trivalent vaccine was studied. The results demonstrate that killed virus vaccine induces and augments NK cell activity for relatively long periods. Such data may prove valuable for designing possible modes of augmenting NK activity as a therapeutic tool.

Adult↗
PubMed1984

Immune reactivity of the tumor-resistant X/Gf mouse.

Parameters of immune reactivity of the tumor-resistant X/Gf mouse have been studied. X/Gf mice show better survival than do control strains following i.p. inoculation with graded doses of YAC lymphoma cells. The natural killer cell activity of X/Gf mice was higher than that of control mice, and this elevated NK activity was inherited by (C57BL/6 X X/Gf)F1 mice. Differences in NK activity of fresh spleen cells from X/Gf, C57BL/6, and (C57BL/6 X X/Gf)F1 mice were not reflected in their ability to lyse in vitro-derived, cloned, transformed cell lines from X/Gf or C57BL/6 mice in an 8 h 51Cr assay; however, the X/Gf-derived malignant cells were more sensitive to lysis than the C57BL/6-derived cells. In order to test whether X/Gf mice demonstrated any exceptional ability to recognize and destroy altered autologous cells, experiments were performed with TNP-modified syngeneic cells. While X/Gf and B10.A effector cells appeared to respond with similar magnitude, hapten-modified X/Gf cells were stronger stimulator cells and more sensitive targets than control strain cells. The ability of X/Gf mice to reject H-2 compatible and incompatible skin grafts is normal, as judged by a comparison of the rejection times with control strains. Allogeneic mixed lymphocyte reactivity, T-cell-mediated lympholysis, delayed-type hypersensitivity reactions, and in vivo phagocytosis of inert particles are of comparable magnitude in X/Gf and control strain mice.

Animals↗
PubMedDate not supplied

The affinity and spectrum of cross reactivity of antibody production in senescent mice: the IgM response.

Experiments were performed to determine whether the IgM component of the primary humoral immune response of senescent mice differs from that of young-adult mice in its affinity, specificity or heterogeneity. For this purpose, mice were immunized with the T-dependent antigen, TNP-KLH, or the T-independent antigen, TNP-LPS. Affinity and specificity of the anti-TNP response were studied at the cellular level by the plaque inhibition technique using the cross-reacting haptens TNP-epsilon-aminocaproic acid )TNP-EACA),DNP-EACA and ONP-EACA. It was found that when the immunogen was TNP-KLH, the peak IgM response was delayed in senescent animals by several days as compared to the response in young adults. However, the number of PFC on the day of peak response was comparable. No age related delay in the peak of response was detected when the antigen was TNP-LPS although the magnitude of response was reduced in old age. The average affinity of the plaque forming cell responses to both immunogens is comparable in young and old mice.

Aging↗
PubMedDate not supplied

T-cell cytotoxicity and aging: differing causes of reduced response in individual mice.

Specific T-cell cytotoxic responses to allogeneic and hapten-modified syngeneic cells decrease with age. In order to determine the causes of these reduced T-cell cytotoxic responses, spleen cells from individual young and senescent C57BL/6J female mice were mixed in various proportions in culture with either X-irradiated BALB/c spleen cells or trinitrophenyl-modified syngeneic cells and the resultant cytotoxic responses determined in comparison to those of spleen cells from young and old mice stimulated alone. In both allogeneic and hapten-modified syngeneic cytotoxicity, it was found that a low percentage of the aged mice suffered from decreased helper-cell activity or from increase of suppressor activity, while the majority of mice showed no synergy, positive or negative, with the cells from the young donor. Studies of interleukin-2 (IL-2) activity were performed on conditioned medium from spleen cells from mice of various ages cultured for 24 h with concanavalin A. Those preparations from senescent mice that showed reduced IL-2 activity did not contain activity suppressive or competitive to IL-2 produced by spleen cells from young mice. Limiting dilution of spleen cells from mice of various ages in the presence of semi-allogeneic stimulatory cells and subsequent assay of the resultant allogeneic cytotoxicity provided a measure of the frequency of cytotoxic units. Parallel experiments in which crude IL-2 was added to the limit dilution cultures provided a measure of the frequency of cytotoxic cell precursors. Once again in these experiments, individual senescent mice demonstrated different defects. Three different types of age-related defects were observed. Certain aged mice were devoid of detectable cytotoxic units and cytotoxic T-lymphocyte precursor at the cell dilutions used. Other senescent mice demonstrated a very low frequency of cytotoxic units (approximately 1/40 000) as compared with young mice (approximately 1/5 000), and the addition of crude IL-2 to cultures from these mice did not improve reactivity. A third group of old mice, those with a moderate age-related decrease in the frequency of cytotoxic units (approximately 1/12 000), demonstrated a cytotoxic T-lymphocyte precursor frequency in the presence of crude IL-2 which was comparable to that of young mice (approximately 1/1000).

Aging↗
PubMedDate not supplied

"The disappearing lens": failure of CT to image the lens in traumatic intumescent cataract.

The CT scans of three patients whose eyes were lacerated by trauma failed to demonstrate the lens. A slit-lamp examination of those eyes clearly indicated that the lenses were present behind the iris but that they were swollen and opaque (intumescent cataract). Apparently, a shift of water into the injured lens had reduced the expected hyperdense CT image of the lens to a level that it was no longer discernible.

Adult↗