CLONAL POPULATIONS OF CD4(-CELLS IN PATIENTS WITH MULTIPLE-MYELOMA AND PARAPROTEINEMIA() AND CD8(+) T)

Patients with paraproteinemia have abnormalities in their T-cell subse ts including inversion of the CD4:CD8 ratio and increased expression o f activation markers. Recently, distortions in T-cell receptor (TCR) T CRAV and TCRBV gene segment expression have been reported, although th e significance of these observations is unclear given the finding of c lonal populations of CD8(+) T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal anti bodies to assess TCRAV and TCRBV expression in patients with myeloma a nd paraproteinemia. TCR sequence analysis was used to assess the clona lity of expansions and 3-color fluorescence-activated cell sorting ana lysis determined the phenotype of the expanded populations. The patien ts show novel oligoclonal expansions within the CD4(+) subset and show an increased frequency of CD8(+) expansions. Oligoclonal CD4(+) T cel ls belong to the rare CD4(+)CD28(-) T-cell subset, a phenotype associa ted with granular morphology. CD45RA and CD11b are expressed on many o f the CD8 T-cell expansions. Comparison of T-cell receptor sequences f rom two T-cell clones in one patient suggests a possible role for a co mmon peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell pro liferation. (C) 1996 by The American Society of Hematology.