Determination of T-cell receptors of clonal CD8-positive T-cells in myelodysplastic syndrome with erythroid hypoplasia.
We determined T-cell receptor alpha-chain variable (TCRAV) and T-cell receptor beta-chain variable (TCRBV) region repertoires in peripheral bloods from patients with myelodysplastic syndrome (MDS) with erythroid hypoplasia. T-cells bearing TCR ADV14S1/BV5S2, AV21S1/BV21S4, and AV2S2/BV7S2 segments were markedly increased in three of four MDS patients, respectively. In addition, there was a positive relationship between the increase in the number of CD8-positive T-cells and the expression levels of these TCR transcripts. These findings suggest that CD8-positive T-cells monoclonally or oligoclonally expanded in the peripheral blood. We also determined the nucleotide and amino acid sequences of the complementarity-determining region 3 (CDR3) of TCR alpha- and beta-chains of the expanded T-cells. Unique sequences were detected in a high percentage of the respective CDR3 clones. The gene segment of the variable and joining regions, however, varied among the patients. The deduced amino acid sequences of CDR3 were heterogeneous among the patients, and there was no common motif. These results indicate there is monoclonal or oligoclonal proliferation of CD8-positive T-cells in MDS patients with erythroid hypoplasia, and suggest that these proliferating T-cells are responsible for the pathogenesis of the MDS entity.
Matsutani
Takaji
T
Department of Medical Science, Discovery Research Laboratories, Shionogi & Co. Ltd., Osaka 566-0022, Japan.
Yoshioka
Takeshi
T
Tsuruta
Yuji
Y
Shimamoto
Takashi
T
Ohyashiki
Junko H
JH
Suzuki
Ryuji
R
Ohyashiki
Kazuma
K
D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007945:Leukemia, Lymphoid / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D017422:Sequence Analysis, DNA
D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell