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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
Statement of
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.
RMID: 0020113671
DOI: 10.4049/jimmunol.1101202
Appears in Collections:Medicine publications

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