Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells : evidence from myeloma-bearing mouse model
Freeman, Lisa M., Lam, Alfred King-Yin, Petcu, Eugene, Smith, Robert A., 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 N., & Vuckovic, Slavica (2011) Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells : evidence from myeloma-bearing mouse model. The Journal of Immunology, 187(8), pp. 3987-3996.
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 CD8alphaalpha 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-gamma 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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|Item Type:||Journal Article|
|Additional Information:||Articles free to read on journal website after 12 months|
|Keywords:||Adoptive Transfer, Animals, CD4-Positive T-Lymphocytes/ immunology, CD8-Positive T-Lymphocytes/ immunology, Cell Line, Tumor, Cell Separation, Cytotoxicity, Immunologic/immunology, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Graft vs Tumor Effect/ immunology, Humans, Immunohistochemistry, Mice, Mice, Inbred NOD, Mice, SCID, Multiple Myeloma/ immunology, Transplantation, Homologous|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 American Association of Immunologists|
|Deposited On:||04 Aug 2014 00:58|
|Last Modified:||06 Feb 2015 04:58|
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