|
|
Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-01-0150.

Submitted January 17, 2003
Accepted June 12, 2003
Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation
Katayoun Rezvani*, Matthias Grube, Jason M Brenchley, Giuseppe Sconocchia, Hiroshi Fujiwara, David A Price, Emma Gostick, Ko Yamada, Jan Melenhorst, Richard Childs, Nancy Hensel, Daniel C Douek, and A J Barrett
Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, USA
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom
* Corresponding author; email: rezvanik{at}nhlbi.nih.gov.
Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1 and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative PCR (qPCR) to measure interferon-gamma (IFN- ) mRNA production by peptide-pulsed CD8+ T cells from HLA-A*0201+ healthy volunteers and CML patients before and after allogeneic stem cell transplantation (SCT). Parallel assays using CMV pp65 tetramers demonstrated the IFN- copy number to be linearly related to the frequency of tetramer-binding T cells, sensitive to frequencies of 1 responding CD8+ T cell/100,000 CD8+ T cells. Responses to WT1 and PR1 but not BCR-ABL were detected in 10/18 healthy donors. Responses to WT1, PR1 or BCR-ABL were observed in 9/14 CML patients pre-SCT and 5/6 post SCT, often to multiple epitopes. Responses were higher in CML patients compared to healthy donors and highest after SCT. These antigen specific CD8+ T cells comprised central memory (CD45RO+CD27+CD57-) and effector memory(CD45RO-CD27-CD57+) T cells. In conclusion, leukemia reactive CD8+ T cells derive from memory T cells and occur at low frequencies in healthy individuals and at higher frequencies in CML patients. The increased response in patients post-SCT suggests a quantitative explanation for the greater effect of allogeneic SCT.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
Related Letter in Blood Online:
-
BCR-ABLspecific T cells can be detected in healthy donors and in chronic myeloid leukemia patients following allogeneic stem cell transplantation
- Nauman M. Butt, Lihui Wang, Hazem M. Abu-Eisha, Steve E. Christmas, and Richard E. Clark
Blood 2004 103: 3245.
[Full Text]
[PDF]
This article has been cited by other articles:

|
 |

|
 |
 
C. Chaise, S. L. Buchan, J. Rice, J. Marquet, H. Rouard, M. Kuentz, G. E. Vittes, V. Molinier-Frenkel, J.-P. Farcet, H. J. Stauss, et al.
DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance
Blood,
October 1, 2008;
112(7):
2956 - 2964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Barrett
Leukemia Vaccines to Boost the Graft-versus-Leukemia Effect after Allogeneic Stem Cell Transplantation
ASCO Educational Book,
January 1, 2008;
2008(1):
330 - 333.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Rezvani, A. S. M. Yong, S. Mielke, B. N. Savani, L. Musse, J. Superata, B. Jafarpour, C. Boss, and A. J. Barrett
Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies
Blood,
January 1, 2008;
111(1):
236 - 242.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Rezvani, A. S. M. Yong, B. N. Savani, S. Mielke, K. Keyvanfar, E. Gostick, D. A. Price, D. C. Douek, and A. J. Barrett
Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia
Blood,
September 15, 2007;
110(6):
1924 - 1932.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. M. Yong, K. Rezvani, B. N. Savani, R. Eniafe, S. Mielke, J. M. Goldman, and A. J. Barrett
High PR3 or ELA2 expression by CD34+ cells in advanced-phase chronic myeloid leukemia is associated with improved outcome following allogeneic stem cell transplantation and may improve PR1 peptide-driven graft-versus-leukemia effects
Blood,
July 15, 2007;
110(2):
770 - 775.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Grube, S. Moritz, E. C. Obermann, K. Rezvani, A. Mackensen, R. Andreesen, and E. Holler
CD8+ T cells Reactive to Survivin Antigen in Patients with Multiple Myeloma
Clin. Cancer Res.,
February 1, 2007;
13(3):
1053 - 1060.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Asemissen, U. Keilholz, S. Tenzer, M. Muller, S. Walter, S. Stevanovic, H. Schild, A. Letsch, E. Thiel, H.-G. Rammensee, et al.
Identification of a Highly Immunogenic HLA-A*01-Binding T Cell Epitope of WT1
Clin. Cancer Res.,
December 15, 2006;
12(24):
7476 - 7482.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al.
BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia.
J. Immunol.,
April 15, 2006;
176(8):
5108 - 5116.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Boissel, P. Rousselot, E. Raffoux, J.-M. Cayuela, J. Soulier, N. Mooney, D. Charron, H. Dombret, A. Toubert, and D. Rea
Imatinib mesylate minimally affects bcr-abl+ and normal monocyte-derived dendritic cells but strongly inhibits T cell expansion despite reciprocal dendritic cell-T cell activation
J. Leukoc. Biol.,
April 1, 2006;
79(4):
747 - 756.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Gillmore, S.-A. Xue, A. Holler, J. Kaeda, D. Hadjiminas, V. Healy, R. Dina, S. C. Parry, I. Bellantuono, Y. Ghani, et al.
Detection of Wilms' Tumor Antigen-Specific CTL in Tumor-Draining Lymph Nodes of Patients with Early Breast Cancer
Clin. Cancer Res.,
January 1, 2006;
12(1):
34 - 42.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Rezvani, J. M. Brenchley, D. A. Price, Y. Kilical, E. Gostick, A. K. Sewell, J. Li, S. Mielke, D. C. Douek, and A. J. Barrett
T-Cell Responses Directed against Multiple HLA-A*0201-Restricted Epitopes Derived from Wilms' Tumor 1 Protein in Patients with Leukemia and Healthy Donors: Identification, Quantification, and Characterization
Clin. Cancer Res.,
December 15, 2005;
11(24):
8799 - 8807.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Sloand, L. Mainwaring, M. Fuhrer, S. Ramkissoon, A. M. Risitano, K. Keyvanafar, J. Lu, A. Basu, A. J. Barrett, and N. S. Young
Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome
Blood,
August 1, 2005;
106(3):
841 - 851.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Gannage, M. Abel, A.-S. Michallet, S. Delluc, M. Lambert, S. Giraudier, R. Kratzer, G. Niedermann, L. Saveanu, F. Guilhot, et al.
Ex Vivo Characterization of Multiepitopic Tumor-Specific CD8 T Cells in Patients with Chronic Myeloid Leukemia: Implications for Vaccine Development and Adoptive Cellular Immunotherapy
J. Immunol.,
June 15, 2005;
174(12):
8210 - 8218.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Fujiwara, J. J. Melenhorst, F. El Ouriaghli, S. Kajigaya, M. Grube, G. Sconocchia, K. Rezvani, D. A. Price, N. F. Hensel, D. C. Douek, et al.
In vitro Induction of Myeloid Leukemia-Specific CD4 and CD8 T Cells by CD40 Ligand - Activated B Cells Gene Modified to Express Primary Granule Proteins
Clin. Cancer Res.,
June 15, 2005;
11(12):
4495 - 4503.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Seggewiss, K. Lore, E. Greiner, M. K. Magnusson, D. A. Price, D. C. Douek, C. E. Dunbar, and A. Wiestner
Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner
Blood,
March 15, 2005;
105(6):
2473 - 2479.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. S. Doubrovina, M. M. Doubrovin, S. Lee, J.-H. Shieh, G. Heller, E. Pamer, and R. J. O'Reilly
In vitro Stimulation with WT1 Peptide-Loaded Epstein-Barr Virus-Positive B Cells Elicits High Frequencies of WT1 Peptide-Specific T Cells with In vitro and In vivo Tumoricidal Activity
Clin. Cancer Res.,
November 1, 2004;
10(21):
7207 - 7219.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. E. Foster, M. Marangolo, M. M. Sartor, S. I. Alexander, M. Hu, K. F. Bradstock, and D. J. Gottlieb
Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion
Blood,
October 15, 2004;
104(8):
2403 - 2409.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Stelljes, R. Strothotte, H.-G. Pauels, C. Poremba, M. Milse, C. Specht, J. Albring, G. Bisping, C. Scheffold, T. Kammertoens, et al.
Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets
Blood,
August 15, 2004;
104(4):
1210 - 1216.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Savage, L. Gao, K. Vento, P. Cowburn, S. Man, N. Steven, G. Ogg, A. McMichael, A. Epenetos, E. Goulmy, et al.
Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen
Blood,
June 15, 2004;
103(12):
4613 - 4615.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. M. Butt, L. Wang, H. M. Abu-Eisha, S. E. Christmas, and R. E. Clark
BCR-ABL-specific T cells can be detected in healthy donors and in chronic myeloid leukemia patients following allogeneic stem cell transplantation
Blood,
April 15, 2004;
103(8):
3245 - 3245.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Fujiwara, F. El Ouriaghli, M. Grube, D. A. Price, K. Rezvani, E. Gostick, G. Sconocchia, J. Melenhorst, N. Hensel, D. C. Douek, et al.
Identification and in vitro expansion of CD4+ and CD8+ T cells specific for human neutrophil elastase
Blood,
April 15, 2004;
103(8):
3076 - 3083.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Grube, K. Rezvani, A. Wiestner, H. Fujiwara, G. Sconocchia, J. J. Melenhorst, N. Hensel, G. E. Marti, L. W. Kwak, W. Wilson, et al.
Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies
Clin. Cancer Res.,
February 1, 2004;
10(3):
1047 - 1056.
[Abstract]
[Full Text]
[PDF]
|
 |
|
| |