Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8+CD57+CD28- compartment

The occurrence of clonal T cells in multiple myeloma (MM), as defined by the presence of rearrangements in the T-cell\ud receptor (TCR)–b chains detected on Southern blotting, is associated with an improved prognosis. Recently, with the\ud use of specific anti–TCR-variable-b (anti–\ud TCRVb) antibodies, the presence in MM patients of expanded populations of T cells expressing particular Vb regions was\ud reported. The majority of these T-cell expansions have the phenotype of cytotoxic T cells (CD81CD571 and perforin\ud positive). Since Vb expansions can result from either a true clonal population or a polyclonal response, the clonality of CD81TCRVb 1 T cells was tested by TCRVb\ud complementarity-determining region 3 length analysis and DNA sequencing of the variable region of the TCR. In this\ud report, the CD571 and CD572 subpopulations within expanded TCRVb 1CD81 cell populations are compared, and it is demonstrated that the CD571 subpopulations are generally monoclonal or biclonal, whereas the corresponding CD572 cells are frequently polyclonal. The oligoclonality\ud of CD571 expanded CD81 T cells but not their CD572 counterparts was also observed in age-matched controls, in\ud which the T-cell expansions were mainly CD82. The CD81CD571 clonal T cells had a low rate of turnover and expressed\ud relatively lower levels of the apoptotic marker CD95 than their CD572 counterparts. Taken together, these findings demonstrate that MM is associated with CD571CD81 T-cell clones, raising the possibility that the expansion and accumulation of activated clonal CD81 T cells in MM may be the result of persistent stimulation by tumor-associated antigens, combined with a reduced cellular death rate\ud secondary to reduced expression of the apoptosis-related molecule CD95. (Blood, 2001;98:2817-2827