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Eur J Immunol ; 40(10): 2720-30, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20836157

ABSTRACT

Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease of hematopoietic stem cells. The disease progresses after several years from an initial chronic phase to a blast phase. Leukemia-specific T cells are regularly detected in CML patients and may be involved in the immunological control of the disease. Here, we analyzed the role of leukemia-specific CD8(+) T cells in CML disease control and the mechanism that maintains CD8(+) T-cell immunosurveillance in a retroviral-induced murine CML model. To study antigen-specific immune responses, the glycoprotein of the lymphocytic choriomeningitis virus was used as model leukemia antigen. Leukemia-specific CTL activity was detectable in vivo in CML mice and depletion of CD8(+) T cells rapidly led to disease progression. CML-specific CTL were characterized by the expression of the IL-7 receptor α-chain. In addition, leukemia cells produced IL-7 that was crucial for the maintenance of leukemia-specific CTL and for disease control. Therefore, CML cells maintain the specific CD8(+) T-cell-mediated immune control by IL-7 secretion. This results in prolonged control of disease and probably contributes to the characteristic chronic phase of the disease.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Interleukin-7/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Receptors, Interleukin-7/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Disease Models, Animal , Flow Cytometry , Interleukin-7/genetics , Kaplan-Meier Estimate , Mice , Mice, Inbred C57BL , Mice, Transgenic , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/immunology
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