Immunologic Unresponsiveness to Murine Leukemia Virus Antigens: Mechanisms and Role in Tumor Development

Chieco‐Bianchi, Luigi; Collavo, Dino; Biasi, Giovanni

doi:10.1016/s0065-230x(08)60224-9

Cited by 25 publications

(20 citation statements)

References 112 publications

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“…CTLs have been shown to play a major role in the regression of numerous experimental tumours (Chieco-Bianchi et al, 1988). Our findings provide direct evidence for the generation of CTL specific for H5V tumour antigens as well.…”

Section: Discussionsupporting

confidence: 61%

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Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vízler

Rosato²,

Calderazzo³

et al. 1998

Br J Cancer

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Summary In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-y monoclonal antibody (MAb) co-administration. These results strongly suggest that the antitumour effect of IL-12 is principally mediated by IFN-y release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis.

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Section: Discussionsupporting

confidence: 61%

“…As anti-tumour cytotoxic T-lymphocyte (CTL) activity may be the basis of an effective immunity to solid tumours of viral origin, our primary aim was to demonstrate the presence of H5V-specific CTLs in the tumour-bearing mice (Chieco-Bianchi et al, 1988).…”

mentioning

confidence: 99%

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Vízler

Rosato²,

Calderazzo³

et al. 1998

Br J Cancer

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“…This because, despite the presence of H-2 d -restricted dominant V␤4 CTL precursors, the H-2 b -restricted CTL would not be as easily evidenced in MLTC in secondary response to MBL-2 (21). The demonstration that spleen cells from M-MSV/MuLV immune B6 mice, after depletion of the V␤5 ϩ subset, were able to differentiate the virus-specific alternative V␤ repertoire in MLTC directly demonstrated that the priming of all the potentially M-MuLV-reactive lymphocytes had occurred.…”

Section: Discussionmentioning

confidence: 99%

“…The injection of transforming M-MSV and its natural MuLV helper gives rise to sarcomas that rapidly undergo spontaneous regression within a few days, mostly due to CD8 response (21). Different MHC class II and I Ag presentation pathways are used in generating virus-specific CTL (22), and a preferential use of specific V␤ chain rearrangements in the H-2 dand H-2 b -restricted CD8 recognition of M-MuLV-induced Ags has been shown (17).…”

mentioning

confidence: 99%

A Large Number of T Lymphocytes Recognize Moloney-Murine Leukemia Virus-Induced Antigens, but a Few Mediate Long-Lasting Tumor Immunosurveillance

Facchinetti

Santa

Mezzalira

et al. 2005

The Journal of Immunology

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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 TCRVβ chain rearrangements. In mice lacking T cells expressing these TCRVβ, we demonstrate that alternative TCRVβ can substitute for the lack of the dominant TCRVβ in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2b-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 Vβ rescues the alternative Vβ response. The mechanism of clonal T cell “immunodomination” that guides the preferential Vβ expansion is likely the result of a proliferative advantage of T cells expressing dominant Vβ, 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, Vβ gene rearrangements. The ability of T cells expressing alternative TCRVβ rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative Vβ 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.

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“…Based on these observations and the demonstration that in vivo protection against viral oncogenesis can be achieved by T lymphocyte adoptive transfer in immunosuppressed mice, it is commonly held that an efficient virus-specific cytotoxic T lymphocyte (CTL) activity plays a major role in clearing the organism of infected cells which represent the target for further neoplastic transformation events (reviewed in Ref. 1).…”

Section: Introductionmentioning

confidence: 99%

Selective Lysis of Activated Cells in Oncorna Virus Infection

et al. 1997

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The authors devised a cytotoxic assay based on cytofluorometric analysis of target surface markers in order to compare lysis exerted in vitro by cytotoxic T lymphocytes (CTLs) on different cell subsets in the context of a single lymphoid target cell population. Using this assay, the authors evaluated when oncorna virus-infected lymphocytes become a suitable target for virus-specific T cell effectors. A lymphocyte population from Moloney-murine leukaemia virus (M-MuLV)-infected (carrier) mice, in which the proliferation of selective Vb T-cell receptor (TCR) families was induced in response to Mls a encoded antigens, was utilized as a target. The authors observed that a virus-specific T cell clone exerted lytic activity preferentially against activated cell subsets. Moreover, virus-specific CTLs generated in mixed leucocyte tumour cell cultures (MLTC) were also able to impair the concomitant anti-Mls a response of lymphocytes from M-MuLV carrier mice. It was found that the proliferative status of oncorna virus-infected target cells played an important role in limiting the in vitro efficacy of the immune response, and it is speculated that this phenomenon might represent an in vivo escape mechanism from immunosurveillance.

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Immunologic Unresponsiveness to Murine Leukemia Virus Antigens: Mechanisms and Role in Tumor Development

Cited by 25 publications

References 112 publications

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity

A Large Number of T Lymphocytes Recognize Moloney-Murine Leukemia Virus-Induced Antigens, but a Few Mediate Long-Lasting Tumor Immunosurveillance

Selective Lysis of Activated Cells in Oncorna Virus Infection

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