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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2892-2900.
Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-01-0150.


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IMMUNOBIOLOGY

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. John Barrett

From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.

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 polymerase chain reaction (qPCR) to measure interferon-{gamma} (IFN-{gamma}) mRNA production by peptide-pulsed CD8+ T cells from HLA-A*0201+ healthy volunteers and from patients with CML before and after allogeneic stem cell transplantation (SCT). Parallel assays using cytomegalovirus (CMV) pp65 tetramers demonstrated the IFN-{gamma} 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 of 18 healthy donors. Responses to WT1, PR1, or BCR-ABL were observed in 9 of 14 patients with CML before SCT and 5 of 6 after SCT, often to multiple epitopes. Responses were higher in patients with CML compared with healthy donors and highest after SCT. These antigen-specific CD8+ T cells comprised central memory (CD45RO+CD27+CD57) and effector memory (CD45ROCD27CD57+) 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 patients with CML. The increased response in patients after SCT suggests a quantitative explanation for the greater effect of allogeneic SCT.


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Related Letter in Blood Online:

BCR-ABL–specific 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]



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