In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma (original) (raw)
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International Journal of Cancer, 1974
BALBIc mice injected with Moloney sarcoma virus (M S V) developed local tumors at the site of inoculation which spontaneously regressed within 20-25 days after injection. Lymphocytes and sera from long-term regressor animals were examined for their specific activities in vitro against Moloney leulcemia virus (M L V) determined antigen (s). Specific activity against the M L V-positive target cells by the lymphocytes from these animals was found to be dependent on the presence of B lymphocytes. In order to investigate some of the possible mechanisms of action of the immune B cells, sera, which were characterized by complement-dependent cytotoxicity, immunofluorescence and virus neutralization, were tested for their ability to stimulate normal syngeneic lymphocytes to be active against the target cells. These antisera placed on the target cells were found to stimulate normal unfractionated or T deprived cells to reduce the targetcell numbers. This effect was not found with normal Tlymphocytes. Time-course kinetics of this antibody-dependent cell-mediated activity in vitro were defined. Adult BALB/c mice injected with Moloney Sarcoma Virus (MSV) develop tumors at thz site of injection with a high incidence of spontaneous regression (Fefer et al., 1967, 1968). Lymphocytes from such animals are active in vitro against target cells possessing the Moloney Leukemia Virus-associated cell-surface antigen(s). This lymphocyte activity has been evalusted by 51Cr release from labelled target cells (Leclerc et al., 1972, 1973) and by reduction of target cell numbers in microcytotoxicity tests (Lamon et al., 1972a,b, 1973a,b). The subpopulations of lymphocytes which are active in this system. have recently begun to be defined (
International Journal of Cancer, 1978
An immunopotentiating factor associated with spleen cells of C57BL/6J mice bearing the 3LL tumor is described. Supernatants of cultured spleen cells from tumor-bearing mice (TBM) augmented the generation of both 19S and 7S antibody-producing cells, when injected with sheep erythrocytes into syngeneic C57BL/6J mice. The enhancing supernatant acted both as a polyclonal activator, when injected in the absence of antigen, and as a potentiator of specific antigen-dependent humoral immune responses, when injected in the presence of antigen. It was found to augment induction of specific memory, but not memory expression. Concomitantly with their influence on humoral immune responses, TBM spleen cell supernatants enhanced tumor growth when injected, mixed with 3LL tumor cells, into syngeneic recipients. The secretion of a factor which augments antibody production was not confined to the 3LL tumor system. Spleen supernatants of C47BL mice carrying the B16 melanoma and those of C3H mice carrying the KHT sarcoma had a similar effect on antibody production. These findings suggest that an immunoregulatory factor(s) appears in spleen cells of TBM as a result of their interaction with the neoplastic tissue. This factor can potentiate production of antibodies, possibly also against tumor-associated antigens. The relevance of the immunopotentiating effects of such factor(s) to tumor growth is discussed.
Journal of Experimental Medicine, 1977
As background for a serological definition of the unique antigens of chemically induced sarcomas, we have typed a series of fibroblast and sarcoma cell lines of BALB/c and C57BL/6 origin by cytoxicity and absorption tests for murine leukemia virus (MuLV)-related cell surface antigens and known alloantigens. 7 of the 17 cultured lines expressed the range of cell surface antigens associated with MuLV (GIX, GCSA, gp70, p30), and this was invariably associated with MuLV production. In nonproducer lines of C57BL/6 (but not BALB/c) origin, a MuLV-gp70-like molecule was found on the surface of fibroblasts and sarcoma cells. The alloantigenic phenotype of these MuLV+ and MuLV- cell lines was H-2D+, H-2K+, Thy-1.2+ or -, PC.1+ or -, Lyt-1.2-, Lyt-2.2-, Ia.7-, and TL.2-. A unique antigen was defined on the BALB/c ascites sarcoma Meth A with antisera prepared in BALB/c or (BALB/c X C57BL/6)F1 mice. Tissue culture lines derived from this tumor were MuLV-, which facilitated serological study of ...
Immunity to MCA‐induced rat sarcomas: Analysis of in vivo and in vitro results
International Journal of Cancer, 1977
Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA-induced sarcomas: (1) post-excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non-crossreactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor-sensitized rats did not demonstrate cell-mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)-proline cytotoxicity assay, spleen cells from FMM3 tumor-bearing rats or from FMM3 tumor-immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3-sensitized rats using the Winn assay and the (3H)-proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti-tumor reactivity was observed only in vivo.
Characterization of T lymphocytes mediatingin vivo protection against RSV-induced murine sarcomas
International Journal of Cancer, 1983
ferent mouse strains share a common tumor-assuciated transplantation antigen, whose expression is controlled both by the viral transforming SK gene and by cellular gene(s) . The mechanism(s) responsible for the in vivo protective immune response against two RSV-induced sarcomas has now been investigated. In the "Winn assay" the growth of both tumors was specifically prevented or significantly reduced by the simultaneous administration of lymphocytes isolated from immunized donors. The effector cells were radiosensitive (2,500 rad), Lyt-I +, Lyt-2,3+ Thy. I + cells. Better protection was afforded by transfer of immune spleen cells from mice pretreated with cyclophosphamide, which is known to abrogate T-cell suppressor activity. In a 5-day mixed lymphocyte/tumor cell culture specific anti-RSV-induced sarcoma cytotoxic activity was barely detected, while a good production of interferon-gamma (IFN-y) was observed. The cells involved showed the same functional and surface phenotype as displayed by the effectors of the "Winn" assay. It is concluded that in the immune rejection of RSVinduced sarcomas. Lyt-I+, Lyt-2,3+ T cells, rather than cytotoxic T lymphocytes, and lymphokines such as IFN-7 are involved.
Int J Cancer, 1973
The nature of the efector cells detected by the chromium release test ( C R T ) has been studied in BALBIc and C57B1/6 mice bearing murine sarcoma virus ( M S V )induced tumors. Anti-8-CSH immune sera completely inhibited the cytotoxic activity of lymphoid cells in the presence of complement; anti-immunoglobulin sera failed to decrease this activity. No activation of normal non-sensitized lymphoid cells in the presence of heat-decomplemented sera from mice bearing MS V-induced sarcomas could be obtained. Identical results have been found in allogeneic systems with major H-2 histocompatibility antigens. It can be concluded that a thymus-processed lymphoid cell sub-population sharing the 8 antigen is exclusively or very predominantly responsible for the immune cytolysis both in syngeneic tumor systems and in allogeneic transplantation systems.