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Patients with paraproteinemia have abnormalities in their T-cell subsets including inversion of the CD4:CD8 ratio and increased expression of activation markers. Recently, distortions in T-cell receptor (TCR) TCRAV and TCRBV gene segment expression have been reported, although the significance of these observations is unclear given the finding of clonal populations of CD8+ T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal antibodies to assess TCRAV and TCRBV expression in patients with myeloma and paraproteinemia. TCR sequence analysis was used to assess the clonality of expansions and 3-color fluorescence-activated cell sorting analysis determined the phenotype of the expanded populations. The patients show novel oligoclonal expansions within the CD4+ subset and show an increased frequency of CD8+ expansions. Oligoclonal CD4+ T cells belong to the rare CD4+CD28- T-cell subset, a phenotype associated with granular morphology. CD45RA and CD11b are expressed on many of the CD8 T-cell expansions. Comparison of T-cell receptor sequences from two T-cell clones in one patient suggests a possible role for a common peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell proliferation.

Type

Journal article

Journal

Blood

Publication Date

15/04/1996

Volume

87

Pages

3297 - 3306

Keywords

Aged, Amino Acid Sequence, Base Sequence, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Separation, Clone Cells, Flow Cytometry, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Humans, Lymphocyte Count, Middle Aged, Molecular Sequence Data, Multiple Myeloma, Paraproteinemias