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  • Myeloma-Induced Alloreactive T Cells Arising in Myeloma-Infiltrated Bones Include Double-Positive CD8+CD4+ T Cells: Evidence from Myeloma-Bearing Mouse Model

    Author(s)
    Freeman, Lisa M
    Lam, Alfred
    Petcu, Eugene
    Smith, Robert
    Salajegheh, Ali
    Diamond, Peter
    Zannettino, Andrew
    Evdokiou, Andreas
    Luff, John
    Wong, Pooi-Fong
    Khalil, Dalia
    Waterhouse, Nigel
    Vari, Frank
    Rice, Alison M
    Catley, Laurence
    Hart, Derek NJ
    Vuckovic, Slavica
    Griffith University Author(s)
    Lam, Alfred K.
    Ariana, Armin S.
    Year published
    2011
    Metadata
    Show full item record
    Abstract
    The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122+ cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T ...
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    The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122+ cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8+ T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8aa and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8+ T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-? and/or perforin compared with single-positive CD8+ T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.
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    Journal Title
    Journal of Immunology
    Volume
    187
    Issue
    8
    DOI
    https://doi.org/10.4049/jimmunol.1101202
    Copyright Statement
    Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
    Subject
    Immunology
    Publication URI
    http://hdl.handle.net/10072/44072
    Collection
    • Journal articles

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