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 th e presence of rearrangements in the T-cell receptor (TCR)-beta chains detec ted on Southern blotting, is associated with an improved prognosis. Recentl y, with the use of specific anti-TCR-variable-beta (anti-TCRVbeta) antibodi es, the presence in MM patients of expanded populations of T cells expressi ng particular V-beta regions was reported. The majority of these T-cell exp ansions have the phenotype of cytotoxic T cells (CD8(+)CD57(+) and perforin positive). Since V-beta expansions can result from either a true clonal po pulation or a polyclonal response, the clonality of CD8(+)TCRV(beta)(+) T c ells was tested by TCRVbeta complementarity-determining region 3 length ana lysis 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(+) sub populations are generally monoclonal or biclonal, whereas the corresponding CD57(-) cells are frequently polyclonal. The oligoclonality of CD57(+) exp anded CD8(+) T cells but not their CD57(-) counterparts was also observed i n 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 r elatively lower levels of the apoptotic marker CD95 than their CD57(-) coun terparts. Taken together, these findings demonstrate that MM is associated with CD57(+)CD8(+) T-cell clones, raising the possibility that the expansio n and accumulation of activated clonal CD8(+) T cells in MM may be the resu lt of persistent stimulation by tumor-associated antigens, combined with a reduced cellular death rate secondary to reduced expression of the apoptosi s-related molecule CD95. (C) 2001 by The American Society of Hematology.