PERSISTENT CLONAL EXCESS AND SKEWED T-CELL REPERTOIRE IN T-CELLS FROMPATIENTS WITH HAIRY-CELL LEUKEMIA

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. Therefor e, we searched for oligoclonal T-cell populations in the blood and spl eens 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 analy zed after PCR amplification of cDNA using TCRBV subfamily-specific pri mers. T cells from 15 of 25 HCL patients showed clonal excess by the T CR gamma-PCR. In fluorescence-activated cell sorted T-cell subsets, mo re clonal bands were observed than in the unseparated T cells, with mo st 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. Analys is 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 com parison, 6 normal samples (2 spleens and 4 blood samples) showed in on ly 1 blood donor 1 clonal band. Two patients with active HCL but witho ut infections or treatment were tested several times during the course of the disease and showed a complete identical skewed T-cell repertoi re with the same oligoclonal T-cell populations. In conclusion, T cell s in the blood and spleen of HCL patients show impressive abnormalitie s with many oligoclonal T-cell populations and a very restricted and s kewed TCRBV repertoire. (C) 1996 by The American Society of Hematology .