Myeloma-induced alloreactive T cells arising in Myeloma-infiltrated bones include double-positive CD8(+)CD4(+) T cells: evidence from myeloma-bearing mouse model

Freeman, L.M. and Lam, A. and Petcu, E. and Smith, R. and Salajegheh, A. and Diamond, P. and Zannettino, A. and Evdokiou, A. and Luff, J. and Wong, P.F. and Khalil, D. and Waterhouse, N. and Vari, F. and Rice, A.M. and Catley, L. and Hart, D.N.J. and Vuckovic, S. (2011) Myeloma-induced alloreactive T cells arising in Myeloma-infiltrated bones include double-positive CD8(+)CD4(+) T cells: evidence from myeloma-bearing mouse model. Journal of Immunology, 187 (8). pp. 3987-3996. ISSN 0022-1767

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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 CD8 alpha 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. The Journal of Immunology, 2011, 187: 3987-3996.

Item Type: Article
Additional Information: Freeman, Lisa M. Lam, Alfred Petcu, Eugene Smith, Robert 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. J. Vuckovic, Slavica
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Haslinda Lahuddin
Date Deposited: 11 Nov 2013 03:32
Last Modified: 11 Nov 2013 03:32
URI: http://eprints.um.edu.my/id/eprint/8534

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