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|Title:||Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8⁺CD4⁺ T cells: evidence from myeloma-bearing mouse model|
|Other Titles:||Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8(+)CD4(+) T cells: evidence from myeloma-bearing mouse model|
|Citation:||Journal of Immunology, 2011; 187(8):3987-3996|
|Publisher:||Amer Assoc Immunologists|
|Lisa M. Freeman, Alfred Lam, Eugene Petcu, Robert Smith, Ali Salajegheh, Peter Diamond, Andrew Zannettino, Andreas Evdokiou, John Luff, Pooi-Fong Wong, Dalia Khalil, Nigel Waterhouse, Frank Vari, Alison M. Rice, Laurence Catley, Derek N. J. Hart and Slavica Vuckovic|
|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 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 CD8αα 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-γ 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.|
|Keywords:||CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Animals; Mice, Inbred NOD; Humans; Mice; Mice, SCID; Multiple Myeloma; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Adoptive Transfer; Transplantation, Homologous; Flow Cytometry; Cell Separation; Immunohistochemistry; Cytotoxicity, Immunologic; Graft vs Tumor Effect; Female|
|Rights:||Copyright © 2011 by The American Association of Immunologists, Inc.|
|Appears in Collections:||Medicine publications|
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