title: Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8(+)CD57(+)CD28(-) compartment.
abstract: 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.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. d.sze@centenary.usyd.edu.au
authors.forename: D M
authors.initials: DM
authors.lastname: Sze
authors.forename: G
authors.initials: G
authors.lastname: Giesajtis
authors.forename: R D
authors.initials: RD
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Raitakari
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.forename: J
authors.initials: J
authors.lastname: Ho
authors.forename: A G
authors.initials: AG
authors.lastname: Baxter
authors.forename: B
authors.initials: B
authors.lastname: Fazekas de St Groth
authors.forename: A
authors.initials: A
authors.lastname: Basten
authors.forename: D E
authors.initials: DE
authors.lastname: Joshua
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions / Q000032:analysis; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000276:immunology / Q000628:therapy; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology*; D019014:fas Receptor / Q000032:analysis
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens; D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor