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 receptor (TCR)-beta chains detected on Southern blotting, is associated with an improved prognosis. Recently, with the use of specific anti-TCR-variable-beta (anti-TCRV(beta)) antibodies, the presence in MM patients of expanded populations of T cells expressing particular V(beta) regions was reported. The majority of these T-cell expansions have the phenotype of cytotoxic T cells (CD8(+)CD57(+) and perforin positive). Since V(beta) expansions can result from either a true clonal population or a polyclonal response, the clonality of CD8(+)TCRV(beta)(+) T cells was tested by TCRV(beta) complementarity-determining region 3 length analysis and DNA sequencing of the variable region of the TCR. In this report, the CD57(+) and CD57(-) subpopulations within expanded TCRV(beta)(+)CD8(+) cell populations are compared, and it is demonstrated that the CD57(+) subpopulations are generally monoclonal or biclonal, whereas the corresponding CD57(-) cells are frequently polyclonal. The oligoclonality of CD57(+) expanded CD8(+) T cells but not their CD57(-) counterparts was also observed in age-matched controls, in which the T-cell expansions were mainly CD8(-). The CD8(+)CD57(+) clonal T cells had a low rate of turnover and expressed relatively lower levels of the apoptotic marker CD95 than their CD57(-) counterparts. Taken together, these findings demonstrate that MM is associated with CD57(+)CD8(+) T-cell clones, raising the possibility that the expansion and accumulation of activated clonal CD8(+) T cells in MM may be the result of persistent stimulation by tumor-associated antigens, combined with a reduced cellular death rate secondary to reduced expression of the apoptosis-related molecule CD95.