Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A limiting dilution microculture system, supplemented with a source of interleukin-2 (IL-2), was employed to evaluate the frequency of Moloney-murine leukaemia/sarcoma virus (M-MuLV/M-MSV)-specific cytotoxic T-lymphocyte precursors (CTL-p) which also exhibited NK-like activity. Spleen cells, obtained from M-MuLV/M-MSV regressor mice, were restimulated in bulk secondary mixed leucocyte-tumour cell cultures (MLTC), and subsequently plated in a culture medium supplemented with two different supernatants (SN) produced following PMA-stimulation of the same EL-4 thymoma cell line. SN 20, obtained from the cell line maintained in vitro, contained IL-2 and only negligible amounts (less than 3 U/ml) of interferon (IFN), while SN 19, obtained after passage of the ascitic form of EL-4 thymoma in syngeneic mice, contained both IL-2 and IFN in high titres. The frequency of CTL-p specific for MBL-2 lymphoma cells was high and comparable in cultures supplemented with both SN (1/2 X 84 cells and 1/2 X 40 cells, respectively), while the frequency of CTL-p directed against NK-susceptible YAC-1 target cells was low in SN 20 (1/90 cells) and high in SN 19 (1/5 X 40 cells). An analysis of individual microcultures established at low cell dose (1 cell/well) indicated that specific and NK-like activity could be ascribed to the same precursor cells. Furthermore, using different long-term CTL clones, we observed that, after passage in SN 20, double-reactive clones gradually lose the capacity to lyse NK-susceptible targets, while most of MBL-2 specific clones acquired NK-like activity following a few passages in SN 19. Therefore, the induction of NK-like activity is reversible and may be modulated by soluble factors present in supernatant in which CTL clones are maintained. Double-reactive clones were unable to lyse NK-resistant allogeneic tumour cells or normal syngeneic blast cells. A few clones cross-reacting with H-2d alloantigens also exhibited NK-like activity when maintained in SN 19. The different pattern of CTL clone activity was associated with a morphological change in the clones themselves: the acquisition of double activity was accompanied by an increase in cell size and the appearance of numerous cytoplasmic granules. All CTL clones were phenotypically Thy-1+ and Lyt-2+ on indirect immunofluorescence and complement-dependent cytotoxicity investigation.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Reversibility of lymphokine-induced NK-like activity in virus-specific cytotoxic T-lymphocyte clones. 257 29

The role of Ia-positive accessory cells in the generation of a secondary cytotoxic response to tumor-associated antigens induced by Moloney murine sarcoma virus (M-MSV) was evaluated. Spleen cells from M-MSV-immune A.TL mice, depleted of accessory cells by anti-Iak serum plus C treatment and stimulated in secondary mixed leukocyte tumor cell culture (MLTC) with syngeneic Ia-negative A6ATL Moloney leukemic cells, failed to generate virus-specific cytotoxic T lymphocytes (CTL). CTL generation in Ia-depleted MLTC may be reconstituted by the addition of nonimmune Ia-positive spleen or peritoneal cells obtained not only from syngeneic A.TL but also from I-incompatible A.TH mice. This lack of restriction observed in accessory cell function is explained in terms of a nonspecific mechanism of CTL triggering mediated by soluble factors. In fact, IL 2 as well as supernatants obtained from I region-incompatible cultures consisting of M-MSV-immune, Ia-depleted A.TL spleen cells and A.TH Ia-positive cells, reconstituted secondary virus-specific CTL generation.
...
PMID:Role of accessory cells in the induction of a secondary cytotoxic response to Moloney murine sarcoma virus-induced tumors. 618 89

To specify the mechanism whereby inoculation of sarcoma viruses protects against leukemia development by leukoviruses, several experiments were performed using Friend virus complex (FVC) and MSV-F, a sarcoma virus pseudotype prepared in vitro with FVC as source of the helper component. The sarcomatous lesions induced by MSV-F were self-limited, irrespective of dose and route of inoculation and protected against the progressive, lethal erythroleukemia induced fy FVC. The sera of MSV-F primed mice had high FVC-neutralizing titers, Out of 3 properties titered in FVC, immunogenicity, XC-syncytium-forming activity and lethality, the frmer two were retained at high titers in MSV-F, while lethality was almost entirely lost: the dose-range between lethal immunizing dilutions was 2-3 logs broader for MSV-F than for FVC. It is postulated that the lethal, early erythroleukemia inducing component (Spleen Focus Forrming Virus) is rapidly lost from FVC upon in vitro propagation. The rescued MSV-F would carry a hightitered, immunogenic and Xc-syncytium forming component (Lymphatic Leukemia Virus), thus behaving as an immunogenic virus of limited pathogenicity.
...
PMID:Immunity to Friend virus complex: analysis of protection with a sarcoma virus pseudotype. 625 97

The distribution of in vitro-stimulated immune lymphocytes in tumor-bearing mice was studied. Spleen cells from BALB/c mice which had regressed Moloney murine sarcoma virus (M-MSV)-induced primary tumors, were sensitized in vitro by using Moloney murine leukemia virus-induced BALB/c lymphoma (LSTRA). Lymphocytes obtained 6 days after stimulation were examined for cytotoxic activity against LSTRA cells, labeled with 51 Cr or 99mTc, and inoculated into mice bearing MSv-induced primary tumors. The distribution of 52Cr-labeled lymphocytes was determined by counting the radioactivity of each organ. Compared to normal lymphocytes, in vitro-stimulated lymphocytes accumulated significantly in tumor tissues and lymphatic organs. The accumulation of MSV-immune lymphocytes in tumor tissues was not evident in 3-methylcholanthrene-induced BALB/c fibrosarcoma, suggesting the operation of specific mechanisms of accumulation of immune lymphocytes. Scintigraphy was performed by inoculating the 99mTc-labeled lymphocytes via the tail vein the tumor-bearing mice. Visualization of the tumor was possible in mice given in vitro-stimulated lymphocytes.
...
PMID:Distribution of in vitro-stimulated immune lymphocytes in mice bearing Moloney murine sarcoma virus-induced primary tumor. 727 51

Local IL-2 administration prior to transplantation of murine sarcoma virus (MSV Harvey)-induced tumour MSVT2 provided a model of slowly growing tumours suitable for long-term investigation of the therapeutic efficacy of repeated IL-2 injection cycles. Challenge of mice with the dose of sarcoma cells, which was lethal for 20/20 untreated control recipients, revealed that 8/20 IL-2-pretreated mice were protected by the local IL-2 treatment and survival indefinitely. Nine out of twenty IL-2-pretreated mice died during the same time period as the control mice, i.e., during 36 days, and 3/20 IL-2 pretreated mice were tumour-negative until day 60, when incipient tumours arose. The three late tumours were used as a model to investigate the therapeutic efficacy of the new cycles of repeated local IL-2 administration. It was found that no resistance to IL-2 immunotherapy was induced by pretreatment of the late tumours and that the tumours were repeatedly susceptible to local IL-2 treatment. Spleen cells of the tumour-bearing mice, which were not cytotoxic for MSVT2 tumour cells in vitro, could be made cytotoxic by addition of exogenous IL-2.
...
PMID:Therapeutic efficacy of repeated cycles of local IL-2 injections in mice carrying slowly growing tumour grafts. 792 62