Role of interferon-alpha and clonally expanded T cells in the immunotherapy of chronic myelogenous leukemia.
Twenty five percent of patients in the chronic phase of chronic myelogenous leukemia (CML) are treated with interferon-alpha (IFN-alpha) to induce a cytogenic remission. In addition to its direct effects on leukemic cells, IFN-alpha has been shown to induce immunologic alterations, including upregulation of the expression of major histocompatibility (MHC) antigens in antigen-presenting cells (APCs), as well as augmentation of the activity of the lymphocytes against tumor cells. However, there has been little direct evidence supporting a causal interaction between cellular immunoreactivity and clinical responsiveness to IFN-alpha. We have shown that one approach to elucidate the immunological mechanisms by which IFN-alpha exerts its anti-CML activity is by analyzing therapy-induced modulation in T-cell receptor (TCR) Vbeta chain usage, using the reverse transcription-polymerase chain reaction (RT-PCR) followed by single-strand conformation (SSCP) analysis. This method is particularly attractive, since it provides an index of antigen-specific T cell expansion, but does not require the extraction and purification of the antigens involved in the T-cell response. T cell clones that express the Vbeta 10, 12, and 14 families predominate in the peripheral blood (PB) of CML patients. The enhanced expression of the Vbeta 9 and 20 families has been detected in IFN-alpha responsive patients but not patients who are poorly responsive to this agent. This suggests that expansion of T cells expressing these TCR Vbeta gene families may serve as a prognostic factors of the clinical responsiveness of CML patients to IFN-alpha. In addition, since T cell clones that express certain Vbeta families may react with a discrete set of antigenic peptides presented on the surface of malignant cells, a better understanding of the immunobiology of T cells in CML may allow for the design of increasing efficacious immune therapy for this disease.
Fujii
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The Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Japan. fujii1018@aol.com
D017951:Antigen Presentation; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D016898:Interferon-alpha