Blood Journal
Leading the way in experimental and clinical research in hematology

Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8+CD57+CD28 compartment

  1. Daniel M.-Y. Sze,
  2. Gillian Giesajtis,
  3. Ross D. Brown,
  4. Maria Raitakari,
  5. John Gibson,
  6. Joy Ho,
  7. Alan G. Baxter,
  8. Barbara Fazekas de St Groth,
  9. Antony Basten, and
  10. Douglas E. Joshua
  1. 1 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.

Abstract

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.

  • Submitted August 17, 2000.
  • Accepted June 26, 2001.
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