title: Persistent clonal excess and skewed T-cell repertoire in T cells from patients with hairy cell leukemia.
abstract: Hairy cell leukemia (HCL) is characterized by a severe T-cell-mediated immune deficiency. At the same time, spontaneous T-cell activation is noted when splenic T cells are studied in vivo and in vitro. Therefore, we searched for oligoclonal T-cell populations in the blood and spleens of 25 patients with HCL using a T-cell receptor gamma-polymerase chain reaction (TCR gamma-PCR). Subsequently, in 6 patients, the CDR3 length and conformation from 22 different TCRBV subfamilies were analyzed after PCR amplification of cDNA using TCRBV subfamily-specific primers. T cells from 15 of 25 HCL patients showed clonal excess by the TCR gamma-PCR. In fluorescence-activated cell sorted T-cell subsets, more clonal bands were observed than in the unseparated T cells, with most of these in CD8+ subsets, but also in CD4+, CD3+ gamma/delta+, and a double-negative CD3+ alpha/beta+ subset. In other B-cell malignancies, 6 of 16 samples showed oligoclonal T cells, whereas only 2 of 18 normal spleen and blood samples showed abnormal bands. Analysis of the TCRBV subfamilies disclosed in all 6 HCL patients a markedly abnormal pattern, with many clonal bands in 5 to 15 subfamilies, and absent or abnormal weak patterns in another 1 to 8 subfamilies. In comparison, 6 normal samples (2 spleens and 4 blood samples) showed in only 1 blood donor 1 clonal band. Two patients with active HCL but without infections or treatment were tested several times during the course of the disease and showed a complete identical skewed T-cell repertoire with the same oligoclonal T-cell populations. In conclusion, T cells in the blood and spleen of HCL patients show impressive abnormalities with many oligoclonal T-cell populations and a very restricted and skewed TCRBV repertoire.
authors.affiliation: Department of Hematology, Leiden University Hospital, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Kluin-Nelemans
authors.forename: M G
authors.initials: MG
authors.lastname: Kester
authors.forename: J J
authors.initials: JJ
authors.lastname: Melenhorst
authors.forename: J E
authors.initials: JE
authors.lastname: Landegent
authors.forename: L
authors.initials: L
authors.lastname: van de Corput
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D001483:Base Sequence; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D007943:Leukemia, Hairy Cell / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell