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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2817-2827
NEOPLASIA
Clonal cytotoxic T cells are expanded in myeloma and reside in
the CD8+CD57+CD28 compartment
Daniel M.-Y. Sze,
Gillian Giesajtis,
Ross D. Brown,
Maria Raitakari,
John Gibson,
Joy Ho,
Alan G. Baxter,
Barbara Fazekas de
St Groth,
Antony Basten, and
Douglas E. Joshua
From the Institute of Haematology, Royal Prince Alfred
Hospital, Camperdown, New South Wales, Australia; Centenary Institute
of Cancer Medicine and Cell Biology, Newtown, New South Wales,
Australia; and the Department of Clinical Chemistry, Turku University
Central Hospital, Turku, Finland.
The occurrence of clonal T cells in multiple myeloma (MM), as
defined by the presence of rearrangements in the T-cell receptor (TCR)- chains detected on Southern blotting, is associated with an
improved prognosis. Recently, with the use of specific
anti-TCR-variable- (anti-TCRV ) antibodies, the
presence in MM patients of expanded populations of T cells expressing
particular V regions was reported. The majority
of these T-cell expansions have the phenotype of cytotoxic T cells
(CD8+CD57+ and perforin positive). Since
V expansions can result from either a true clonal
population or a polyclonal response, the clonality of
CD8+TCRV+ T cells was tested by
TCRV 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+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.
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