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https://hdl.handle.net/2440/68146
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dc.contributor.author | Freeman, L. | - |
dc.contributor.author | Lam, A. | - |
dc.contributor.author | Petcu, E. | - |
dc.contributor.author | Smith, R. | - |
dc.contributor.author | Salajegheh, A. | - |
dc.contributor.author | Diamond, P. | - |
dc.contributor.author | Zannettino, A. | - |
dc.contributor.author | Evdokiou, A. | - |
dc.contributor.author | Luff, J. | - |
dc.contributor.author | Wong, P. | - |
dc.contributor.author | Khalil, D. | - |
dc.contributor.author | Waterhouse, N. | - |
dc.contributor.author | Vari, F. | - |
dc.contributor.author | Rice, A. | - |
dc.contributor.author | Catley, L. | - |
dc.contributor.author | Hart, D. | - |
dc.contributor.author | Vuckovic, S. | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Journal of Immunology, 2011; 187(8):3987-3996 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | http://hdl.handle.net/2440/68146 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | 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 | - |
dc.language.iso | en | - |
dc.publisher | Amer Assoc Immunologists | - |
dc.rights | Copyright © 2011 by The American Association of Immunologists, Inc. | - |
dc.source.uri | http://dx.doi.org/10.4049/jimmunol.1101202 | - |
dc.subject | CD4-Positive T-Lymphocytes | - |
dc.subject | CD8-Positive T-Lymphocytes | - |
dc.subject | Cell Line, Tumor | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred NOD | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | Mice, SCID | - |
dc.subject | Multiple Myeloma | - |
dc.subject | Disease Models, Animal | - |
dc.subject | Enzyme-Linked Immunosorbent Assay | - |
dc.subject | Adoptive Transfer | - |
dc.subject | Transplantation, Homologous | - |
dc.subject | Flow Cytometry | - |
dc.subject | Cell Separation | - |
dc.subject | Immunohistochemistry | - |
dc.subject | Cytotoxicity, Immunologic | - |
dc.subject | Graft vs Tumor Effect | - |
dc.subject | Female | - |
dc.title | Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8⁺CD4⁺ T cells: evidence from myeloma-bearing mouse model | - |
dc.title.alternative | Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8(+)CD4(+) T cells: evidence from myeloma-bearing mouse model | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.4049/jimmunol.1101202 | - |
dc.relation.grant | NHMRC | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Zannettino, A. [0000-0002-6646-6167] | - |
dc.identifier.orcid | Evdokiou, A. [0000-0001-8321-9806] | - |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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