Dysfunctional T regulatory cells in multiple myeloma

Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (Treg) cells play an important role...

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Bibliographic Details
Published in:Blood 2006-01, Vol.107 (1), p.301-304
Main Authors: Prabhala, Rao H., Neri, Paola, Bae, Jooeun E., Tassone, Pierfrancesco, Shammas, Masood A., Allam, Charles K., Daley, John F., Chauhan, Dharminder, Blanchard, Elizabeth, Thatte, Hemant S., Anderson, Kenneth C., Munshi, Nikhil C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Case-Control Studies
CD4 Lymphocyte Count
Cell Proliferation
Hematologic and hematopoietic diseases
Humans
Immunity, Cellular
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphocyte Activation
Medical sciences
Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma - immunology
Neoplasia
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - pathology
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Summary:Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (Treg) cells play an important role in suppressing normal immune responses, we evaluated the potential role of Treg cells in immune dysfunction in MM. We observed a significant increase in CD4+CD25+ T cells in patients with monoclonal gammopathy of undetermined significance (MGUS) and in patients with MM compared with healthy donors (25% and 26%, respectively, vs 14%); however, Treg cells as measured by FOXP3 expression are significantly decreased in patients with MGUS and MM compared with healthy donors. Moreover, even when they are added in higher proportions, Treg cells in patients with MM and MGUS are unable to suppress anti-CD3–mediated T-cell proliferation. This decreased number and function of Treg cells in MGUS and in MM may account, at least in part, for the nonspecific increase in CD4+CD25+ T cells, thereby contributing to dysfunctional T-cell responses.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-08-3101