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)–β chains detected on Southern blotting, is associated with an improved prognosis. Recently, with the use of specific anti–TCR-variable-β (anti–TCRVβ) antibodies, the presence in MM patients of expanded populations of T cells expressing particular Vβ regions was reported. The majority of these T-cell expansions have the phenotype of cytotoxic T cells (CD8+CD57+ and perforin positive). Since Vβ expansions can result from either a true clonal population or a polyclonal response, the clonality of CD8+TCRVβ+ T cells was tested by TCRVβ 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 TCRVβ+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.