Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome.
Selected patients with Myelodysplastic Syndromes (MDS) are responsive to immunosuppressive therapy, suggesting that hematopoietic suppressive T cells have a pathogenic role in ineffective hematopoiesis. We assessed T-cell receptor (TCR) clonality through combined flow cytometry and molecular analysis of the complementarity determining region (CDR)-3 of the T-cell receptor-Vbeta gene. We identified clonal T cells in 50% of MDS patients (n=52) compared to 5% of age-matched normal controls (n=20). The presence of T-cell clones was not associated with features linked previously to immunosuppression response, including WHO diagnostic category, karyotype, marrow cellularity, IPSS category, sex or age <or=60. Using flow cytometry to identify expanded Vbeta-families, we found that T cells showed greater expansion in the bone marrow compared with peripheral blood, and were characterized as CD8(+)/CD57(+)/CD28(-) effector T cells. Expanded effector T cell were CD62L negative and expressed the natural killer C-lectin-family receptor NKG2D and CD244 (2B4). We conclude that clonal T-cell expansion is common among all MDS prognostic subgroups.
Epling-Burnette
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Immunology Program, H Lee Moffitt Cancer Center, Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL 33612, USA. Pearlie.Burnette@moffitt.org
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Rollison
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Widen
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D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell