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Tumorigenicity of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2Kk antigens

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Abstract

We have previously found that an increased tumorigenicity and spontaneous metastatic potential of BW5147-derived T lymphoma cells was associated with a decrease in major histocompatibility complex (MHC) class I H-2Kk antigen expression. This suggested that H-2Kk antigens may control the tumorigenic potential of BW T lymphoma cells. Our current experiments aimed to prove this association by specifically altering H-2Kk expression by gene transfection. Transfected cells expressing a high level of H-2Kk antigens were significantly less tumorigenic and metastatic after subcutaneous inoculation. However, there was selectionin vivo for cells expressing a reduced level of H-2Kk antigens, which concomitantly led to an increased tumorigenicity. These data further confirmed the strong association between H-2Kk expression and tumorigenicity. We subsequently tested whether the immune system is implicated in this phenomenon by inoculating the H-2Kk transfectants into irradiated, immunocompromised recipients. Our results indicate that the reduced tumorigenicity of the BW H-2Kk transfectants is due to an immune rejection mechanism, mediated by CD8+ immune effector cells, as revealed byin vivo depletion experiments with anti-CD8 antibodies. Hence, we hereby demonstrated that H-2Kk antigens increased the immunogenicity of BW cells, via a CD8-dependent mechanism, which consequently reduced their tumorigenicity.

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Authors and Affiliations

  1. Laboratory of Cellular Immunology, Institute of Molecular Biology, Free University of Brussels, Paardestraat 65, B-1640, Sint-Genesius-Rode, Belgium

    Thierry VandenDriessche &  Patrick De Baetselier

  2. Laboratory of Hematology, Academic Hospital, Free University of Brussels, Jette

    Marleen Bakkus & Kris Thielemans

  3. Pasteur Institute of Brabant, Linkebeek, Belgium

    Dominique Toussaint-Demylle & Hendrik Verschueren

Authors
  1. Thierry VandenDriessche
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  2. Marleen Bakkus
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  3. Dominique Toussaint-Demylle
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  4. Kris Thielemans
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  5. Hendrik Verschueren
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  6. Patrick De Baetselier
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VandenDriessche, T., Bakkus, M., Toussaint-Demylle, D. et al. Tumorigenicity of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2Kk antigens. Clin Exp Metast 12, 73–83 (1994). https://doi.org/10.1007/BF01784336

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  • DOI: https://doi.org/10.1007/BF01784336

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