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E Yefenof

Publications and source records attributed to E Yefenof.

At least 73 records · Page 4Linked to original sources
PubMed1987

A highly leukemogenic radiation leukemia virus isolate is a thymotropic, immunosuppressive retrovirus with a unique RNA structure.

Clones of N-, B- and NB-fibrotropic viruses were isolated from weakly (D-RadLV) and strongly (A-RadLV) leukomogenic RadLV preparations. A highly leukemogenic, thymotropic virus (TV) was isolated by ex-vivo infection of thymocytes with A-RadLV. This virus could not be isolated from D-RadLV. Two-dimensional fingerprint analysis suggested that TV recombines unique RNA sequences with RNA genomic material derived from a B-tropic endogenous virus. C57BL/6 (B6) mice injected with B- or NB-fibrotropic clones, but not with TV or N-tropic viral clones, developed reactive T lymphocytes (Tr), capable of differentiating into anti-tumor cytotoxic cells. The N-tropic virus isolates were non-immunogenic in B6 mice whereas the TV isolate induced suppressor T lymphocytes (Ts) that abrogated a potential Tr response. These results suggest that emergence of highly leukemogenic RadLV involves activation of endogenous fibrotropic virus which is immunogenic in its natural host strain (B6). This virus can further recombine with other retroviral genetic sequences, resulting in a suppressogenic and thymotropic, highly leukemogenic virus.

Animals↗
PubMed1986

In vitro activation of murine antigen-specific memory B cells by a T-dependent antigen.

A procedure that generates an enriched population (60 to 85%) of memory B cells specific for TNP (TNP-MABC) was employed. The activation requirements of TNP-MABC for the T-dependent antigen TNP-KLH and carrier-primed helper T (Th) cells were compared to those for TNP-binding cells from nonimmune mice (TNP-ABC). Proliferation and differentiation of TNP-MABC in response to cognate recognition of antigen requires less antigen and fewer carrier-primed Th cells than the activation of TNP-ABC. Furthermore, responses of the TNP-MABC were of a greater magnitude. Non-cognate activation induces a low level of proliferation of both TNP-ABC and TNP-MABC, but induces differentiation of TNP-MABC only. Percoll density fractionation of spleen cells prior to enrichment for TNP-MABC suggests that the small, dense cell population responds to cognate, but not to non-cognate activation. FACS separation of TNP-MABC by surface Ig isotype reveals that approximately 80% of the secondary IgG response is derived from cells expressing sIgG. Such cells constitute less than 10% of the total number of TNP-MABC. Limiting dilution studies with sorted TNP-MABC indicate that sIgG+ TNP-MABC are enriched for precursors that give rise to a large clone size. The in vitro results indicate the existence of three putative pathways for antigen-specific memory B cell activation by a T-dependent antigen: 1) sIgG+ cells differentiating into IgG-secreting cells; 2) sIgM+ cells differentiating into IgG-secreting cells; and 3) sIgM+ cells differentiating into IgM-secreting cells.

Animals↗
PubMed1986

Immunity and suppression in radiation- and radiation leukemia virus (RadLV)-induced leukemogenesis.

Adult C57BL/6 (B6) mice exposed to fractionated irradiation or inoculated with a highly leukemogenic RadLV (A-RadLV) develop high incidence of lymphatic leukemias after a latency of 3-5 months. Inoculation of a low leukemogenic RadLV variant (D-RadLV) does not result in lymphoma development unless the animals receive a single, sublethal dose of irradiation. Whereas virus-induced primary lymphomas produce virus, express gp70 and are all immunogenic, those induced by X-rays are devoid of virus expression and are not immunogenic. A-RadLV inoculation into B6 mice is associated with early induction of virus specific, cyclophosphamide sensitive suppressor T cells which are capable of abrogating a potential antitumor immune responsiveness. D-RadLV, on the other hand, induces reactive T lymphocytes that arrest leukemogenesis unless their function is impaired by irradiation. In (B6 X BALB/c)F1 mice both A-RadLV and D-RadLV leukemogenesis depend on sublethal irradiation of the host, and both induce reactive T cells. These results suggest that (a) RadLV and X-ray induced leukemogeneses involve different etiologies. (b) Different leukemogenic treatments evoke different host responses early in latency which can either sustain or interfere with lymphoma progression.

Animals↗
PubMed1985

Antigen non-specific activities in culture supernatant of ovalbumin-specific, cloned helper T lymphoma.

Antigen non-specific activities in culture supernatants from clones of a radiation leukemia virus transformed, ovalbumin-specific helper T lymphoma were studied. After stimulation with ovalbumin-pulsed macrophages, these clones release factor(s) capable of providing carrier-specific help for anti-hapten antibody responses. It was found that in addition to IL 2-like activity, one clone constitutively released a suppressive factor that could inhibit polyclonal growth and differentiation of B cells stimulated with LPS. The factor inhibited activation of both syngeneic and allogeneic B cells directly, rather than via activation of accessory suppressor T lymphocytes. However, upon dilution of the supernatant, B cell growth and differentiation activities were detected. A role for a polyclonal B cell suppressor factor in the overall helper activity of the clone is proposed.

Animals↗
PubMed1985

Complement-dependent cellular cytotoxicity: lymphoblastoid lines that activate complement component 3 (C3) and express C3 receptors have increased sensitivity to lymphocyte-mediated lysis in the presence of fresh human serum.

Lymphocyte-mediated lysis of cells of the Raji, Daudi, Jijoye, and Bjab lines was elevated when fresh human serum was added to the assay. A higher proportion of effector-target conjugates was observed in the presence of human serum. In similar experiments lysis of 1301, Rael, and P3HR-1 cells was unaltered. All cell lines activated the alternative pathway of complement but they varied in the expression of receptors for complement component 3 (C3) and in the ability to fix the C3 cleavage products on their membrane. The enhancement of lysis in the presence of human serum occurred only with those cells that bound C3. This characteristic was correlated to the expression of C3 receptors. Analysis of the nature of the deposited C3 was performed with Raji cells. Raji cells exposed to human serum bound C3b as indicated by the immunoadherence test. The C3b was further processed to C3bi, because the immunoadherence declined with time and conjugate formation increased with Daudi cells, which carry the C3 receptors CR2 and CR3. This suggests that in the lytic assay lymphocytes with C3bi receptors are recruited in the presence of human serum. We assume that the bridge of C3 molecules between targets and effectors increases the avidity of their interaction.

Burkitt Lymphoma↗
PubMed1985

Preparation and analysis of antigen-specific memory B cells.

A procedure has been developed for the enrichment of TNP-binding memory B cells (TNP-MABC) from spleens of immunized mice. More than 75% of the cells expressed surface IgM (sIgM) and IgD (sIgD) and about 9% expressed surface IgG (sIgG). The TNP-MABC consisted of small resting lymphocytes with high affinity antigen-binding receptors. These cells expressed increased densities of Ia antigens and decreased densities of sIgD. Adoptive transfer of the cells into irradiated, carrier-primed syngeneic recipients resulted in their differentiation into IgG anti-TNP antibody-secreting cells. TNP-MABC secreted high affinity IgG anti-TNP antibodies when cultured in vitro with carrier-primed T cells and antigen. Limiting dilution analysis revealed that TNP-MABC contained a relatively low frequency of precursors for IgG-secreting cells that had an exceptionally large clone size. These results show that a highly enriched population of antigen-specific memory B cells can now be prepared and used to analyze their activation requirements.

Animals↗
PubMed1984

High- and low-leukemogenic variants of the radiation leukemia virus (RadLV): immunogenic, suppressive and genetic properties in relation to leukemogenic activity.

C57BL/6 (B6) mice inoculated with the highly leukemogenic variant of the radiation leukemia virus (A-RadLV) develop suppressor cells capable of abrogating potential anti-tumor immunity in vitro and in vivo. Inoculation of B6 animals with the low-leukemogenic D-RadLV variant does not result in suppressor cell generation but induces antitumor reactive lymphocytes. A-RadLV and D-RadLV are not leukemogenic in BALB/c or (B6 X BALB/c)F1(F1) mice, and reactive but not suppressor lymphocytes could be demonstrated in F1 animals inoculated with either virus. Infectivity assays and fingerprint analysis revealed that A-RadLV and D-RadLV contain viruses with N and B tropism. In addition, thymoma cells induced by A-RadLV produced another virus with a fingerprint pattern containing X-MuLV elements. The possible implications of the different virus types on the immunogenic and leukemogenic properties of the RadLV variants are discussed.

Animals↗
PubMed1984

Complement-dependent cellular cytotoxicity due to alternative pathway C3 activation by the target cell membrane.

The cytotoxic activity of human blood lymphocytes toward Raji cells was strongly elevated when human serum (HS) was included in the cytotoxicity assay. This phenomenon also occurred when the effector cells were activated by interferon (IFN). Hypogammaglobulinemic serum (HyS) and heat-inactivated serum could also augment cytotoxicity, but C3-depleted serum was inefficient. IFN treatment of Raji cells decreased their sensitivity to lysis and this effect was counteracted by addition of HS to the system. It is likely that C3 activation by, and deposition on, Raji cells when used as targets for cytotoxicity facilitate their recognition and lysis by lymphocytes. These events may represent one mechanism operating in the natural killing phenomenon.

Complement Activation↗
PubMed1984

Contribution of activated C3 to lymphocyte-mediated target lysis: complement-dependent cellular cytotoxicity.

Lysis of Raji cells by human lymphocytes was found to be enhanced if human serum was added to the assay. This was not due to the contribution of antibodies because hypogammaglobulinemic serum also augmented cytotoxicity. The results suggest that the mechanism of the enhancement was due to activation of C3 by the Raji cells. We assume that the cleavage products are deposited on cell surfaces in such a way that they contribute to contact between effector and target. Previous reports in two antibody-dependent cellular cytotoxicity systems provided other examples for the existence of this phenomenon.

Blood↗
PubMed1983

Suppressor and reactive lymphocytes in radiation leukemia virus (RadLV)-induced leukemogenesis.

Suppressor cells capable of enhancing tumor growth in vivo and of abrogating a potential anti-tumor immunity in vitro are generated in C57BL/6 mice inoculated with the high-leukemogenic A-RadLV. Mice inoculated with low-leukemogenic D-RadLV do not develop suppressor cells but contain anti-tumor reactive lymphocytes that can inhibit in vivo tumor growth. Cyclophosphamide (CyF) treatment of mice inoculated with A-RadLV hampered suppressor cell function and rendered the animals' lymphocytes responsive to A-RadLV induced tumor cells in vitro. Administration of CyF also reduced leukemia incidence in mice inoculated with A-RadLV, but had no effect on leukemia induction by D-RadLV in irradiated mice. It is suggested that the high leukemogenic activity of A-RadLV depends on the virus' ability to recruit CyF-sensitive suppressor cells early in latency and that tumor progression in mice inoculated with D-RadLV is arrested due to the host immune response.

Animals↗
PubMed1983

Increased humoral and cellular immunity in mice inoculated with allogeneic tumor cells attached to microcarrier beads.

A murine carcinoma cell line was grown in a microcarrier culture and was used for immunization of allogeneic mice. It was found that inoculation of cells attached to microcarrier beads resulted in heightened serum titers of cytotoxic antibodies and in a stronger cell-mediated cytotoxic reactivity in the spleen compared to cells detached from the substrate. It is proposed that immunization of animals with anchorage-dependent cells should be carried out while the cells are still adherent to the culture microcarriers.

Animals↗
PubMed1982

High- and low-leukemogenic variants of the radiation leukemia virus (RadLV) differ in ability to induce tumor-specific immune suppression.

Adult C57BL/6 mice inoculated intrathymically (i.t.) with the highly leukemogenic variant of the radiation leukemia virus (A-RadLV) develop suppressor cells capable of specifically abrogating a potential anti-tumor cytotoxic response in vitro. Suppressor cells were generated directly by the virus, independently of an initiation of a leukemogenic process. Inoculation of C57BL/6 animals with the low leukemogenic D-RadLV variant did not result in suppressor cell generation. It is proposed that induction of tumor-specific immune suppression by A-RadLV is essential for tumor progression, and the leukemogenic activity of D-RadLV is attributed to its inability to recruit suppressor cells.

Animals↗
PubMed1982

Immortalization of antigen specific, helper T cell lines by transformation with the radiation leukemia virus (RadLV).

Antigen-specific immune T lymphocytes of male C57BL/6 mice were enriched in vitro on monolayers of antigen-pulsed syngeneic macrophages. The cells were treated in vitro with RadLV and inoculated intrathymically into irradiated female C56BL/6 animals. Thymomas arising in the inoculated recipients were characterized as donor- (male) type according to their karyotype. In vivo and in vitro cell lines were established from the primary lymphomas, two of which (designated ROT/6.1 and ROT/6.2) were capable of providing antigen- (carrier) specific help in normal or preimmunized mice. None of the lymphomas could induce antigen-specific DTH reaction. Five months after their establishment, ROT/6.2 alone retained its carrier specificity. ROT/6.2 consisted mainly of Lyt-1+ cells, whereas the ROT/6.1 population was more heterogeneous and contained Lyt-1+, Lyt-2+, and Lyt-3+ cells. The carrier specificity of the latter may have been lost due to selection against the specific helper cells during prolonged passages.

Animals↗
PubMed1982

Nonimmunogenic radiation-induced lymphoma: immunity induction by a somatic cell hybrid.

The cell line designated PIR-2 is a nonimmunogenic X-ray-induced thymoma of C57BL/6 origin that is unable to induce antitumor immunity in syngeneic lymphocytes in vitro and in mice in vivo. Fusion of PIR-2 with an allogeneic "universal fuser" A9HT (clone 3c) resulted in the establishment of a somatic cell hybrid designated A9/PIR. C57BL/6 lymphocytes sensitized in vitro with A9/PIR could lyse parental PIR-2 cells, as well as other syngeneic tumors. However, immunization of mice with the hybrid significantly enhanced PIR-2 tumor takes while it partially protected the animals against a challenge with unrelated syngeneic tumors. The results imply that somatic cell hybridization can increase the immunogenicity of an otherwise nonimmunogenic tumor. However, in view of the enhancing effects of hybrid preimmunization on parental tumor cell growth, the possible application of this approach for immunotherapy is questionable.

Animals↗