Induction of Moloney murine sarcoma virus tolerance in adult mice by anti-CD4 monoclonal antibody treatment (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, 1984
It was shown previously that B6.C-H-Zbm" (bm14) mice, carrying a mutation in the H-2Db locus, are unable to generate cytotoxic T cells (CTL) against Moloney murine sarcoma virus (M-MSV). We now report an analysis of tumor induction and regression kinetics and of immunity to the virus, following the injection of graded doses of M-MSV into C57BU6 (B6) and bm 14 mice. Contrary to expectation, bm14 mice showed slightly less tumors than wildtype B6 mice. Moreover, all bm14 mice that developed a tumor were able to reject this tumor, even after injection of the highest virus dose tested. From the spleen cells of bm I4 mice that had rejected tumors, no secondary in vitro CTL responses could be generated, in contrast to strong CTL responses generated from B6 spleen cells. Although bm14 mice were unable to generate virus-specific CTL, they showed nomal antibody and T-cell proliferative responses against Moloney virus, suggesting an intact Thelper-cell function. It is concluded that in bm I4 mice, under the conditions tested, virus-specific CTL are not generated despite excellent tumor immunity. Therefore, this CTL response is not necessary for protection against M-MSV-induced tumors. Protection is likely to be mediated by a normal T-cell proliferative response.
European Journal of Immunology, 1976
Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells* Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)-induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV-associated antigens in secondary mixed leukocyte-tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV-associated antigens. When MSV-immune spleen cells from C57BL/6 (H-2b) and BALB/c (H-2d) mice were compared with respect to their ability t o generate CTL in syngeneic secondary MLTC, it was found that both lymphoid cell populations were equally able t o mount an anamnestic CTL response to MSV-associated antigens as assessed by a short-term 51Cr release assay. However, quantitative analysis of the activity of both CTL populations on either H-2b or H-2d tumor cells indicated that target cells sharing the same major histocompatibility complex (MHC) as the effector cells were lysed 10-to 100-fold more efficiently than allogeneic target cells. As suggested by the results of inhibition experiments using mixtures of 51 Cr-labeled and unlabeled target cells, preferential lysis of syngeneic versus allogeneic tumor cells might be related to the establishment of effective adhesions between the former and CTL. Direct evidence for the role of MHC in determining the antigenic specificity of CTL directed against MSV-associated antigens was provided by results obtained using MSV-immune spleen cells from congenic resistant mice. Furthermore, studies of the response of F , (H-2b/d) hybrid mice showed that stimulation of immune spleen cells with tumor cells from one parental strain or the other in secondary MLTC resulted in the generation of CTL capable of lysing tumor target cells of the same parental strain as the stimulating cells, but not of the other. The results thus suggested the presence of two sets of CTL precursor cells in F, MSV-immune spleens, each set responding exclusively to tumor antigens associated with only one of the two parental phenotypes.
Immune response to Moloney-murine leukemia virus-induced antigens in bone marrow
Immunology Letters, 2011
By exploring induction and persistence of virus-specific memory CD8 + T cells in the BM of Moloneymurine sarcoma/leukemia virus-immune mice, we observed that the amount of activated CD8 + CD62L − cells increased more rapidly and persisted for a longer period than in peripheral organs. Among the CD8 + CD62L − subset, the few cells, specific for M-MuLV encoded antigens, expressing TCRV5 rearrangements increased in an explosive manner doubling the percentage of TCRV5 + subset so that as a final result more than 10% of CD8 + lymphocytes became potential virus-specific cytotoxic effectors. The numerical expansion of V5 + cells started and persisted in the same proportion among both CD8 + CD62L − and CD8 + CD62L + subsets. In these subsets the analysis of CD44 phenotype, to distinguish effector (TEM) and central (TCM) memory, evidenced a twofold increase of V5 + TEM percentage and fourfold increase of V5 + TCM. In parallel, the non virus-specific V5 − counterpart, also numerically increased due to the CD8 + expansion, was partially reduced as TEM percentage and doubled as TCM percentage. We conclude that the immune response to M-MuLV encoded antigens in BM generate not only a large number of virus-specific memory cells but also the re-shaping of the entire memory T cell repertoire.
Drug-mediated immunogenic changes of virus-induced leukemia in vivo
Cancer research, 1976
LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were used to determine whether antigenically altered tumors induced by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo would retain their original antigenic properties and/or have new antigenic properties. The tumors became highly immunogenic in the syngeneic hosts after 4 to 8 transplant generations with drug treatment. Syngeneic mice could be protected against challenge with the parental tumor by presensitization with the drug-altered sublines while unrelated tumor lines were incapable of protecting them. The drug-altered subline of LSTRA was used for treatment of the LSTRA in conjunction with chemotherapy, and this immunochemotherapy produced significant increases in number of survivors and increases in median survival time compared to either treatment alone. Tolerance studies indicated that there are novel antigens and parental tumor antigens associated with the drug-treated sub...
The Journal of Immunology, 2005
The CD8 ؉ T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags is almost entirely dominated by the exclusive expansion of lymphocytes that use preferential TCRV chain rearrangements. In mice lacking T cells expressing these TCRV, we demonstrate that alternative TCRV can substitute for the lack of the dominant TCRV in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2 b -restricted response, the shift of TCR usage is not related to a variation of the immunodominant M-MuLV epitope recognition. After virus immunization, all the potentially M-MuLV-reactive lymphocytes are primed, but only the deletion of dominant V rescues the alternative V response. The mechanism of clonal T cell "immunodomination" that guides the preferential V expansion is likely the result of a proliferative advantage of T cells expressing dominant V, due to differences in TCR affinity and/or cosignal requirements. In this regard, a CD8 involvement is strictly required for the virus-specific cytotoxic activity of CTL expressing alternative, but not dominant, V gene rearrangements. The ability of T cells expressing alternative TCRV rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative V chains were activated and expanded, they were not able to control tumor growth in a long-lasting manner due to their incapacity of conversion and accumulation in the T central memory pool.