Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia.
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.
Moss
P
P
Department of Haematology, Institute of Molecular Medicine, The Churchill Radcliffe Hospital, Headington, Oxford, UK.
Gillespie
G
G
Frodsham
P
P
Bell
J
J
Reyburn
H
H
D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002469:Cell Separation; D002999:Clone Cells / Q000473:pathology*; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D018655:Lymphocyte Count; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology*