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https://hdl.handle.net/2440/68146
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Type: | Journal article |
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 |
Author: | Freeman, L. Lam, A. Petcu, E. Smith, R. Salajegheh, A. Diamond, P. Zannettino, A. Evdokiou, A. Luff, J. Wong, P. Khalil, D. Waterhouse, N. Vari, F. Rice, A. Catley, L. Hart, D. Vuckovic, S. |
Citation: | Journal of Immunology, 2011; 187(8):3987-3996 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2011 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | 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. |
DOI: | 10.4049/jimmunol.1101202 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.4049/jimmunol.1101202 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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