T cell repertoire in patients with multiple myeloma and monoclonal gammopathy of undetermined significance: Clonal CD8+ T cell expansions are found preferentially in patients with a low tumor burden

Eva Halapi, Åsa Werner, Jan Wahlström, Anders Österborg, Mahmood Jeddi-Tehrani, Qing Yi, Carl Harald Janson, Hans Wigzell, Johan Grunewald, Håkan Mellstedt

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The T cell receptor (TCR) variable (V) gene repertoire was analyzed in patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 17), multiple myeloma (MM) stage I (n = 16), MM stages II/III (n = 31) and agematched controls (n = 27) by immunofluorescence and flow cytometry using a panel of mouse monoclonal antibodies (mAb) (n = 10) against TCR Vα and Vβ gene products. T cell expansion was defined as a value ≤ thrice the normal median value for each respective TCR V mAb. Fifty-three percent of all patients displayed CD8+ expansion(s) as compared to 30% of age-matched controls (p < 0.001). Within the CD4 subset, 18% of the patients displayed T cell expansion(s) in comparison to 11% of the controls (not significant). Interestingly the CD8+ expansion(s) were more frequently noted in patients with a low tumor burden (MGUS/MMI) (73%) as compared to those with advanced disease (MM II/III) (32% and control donors (30%) (p < 0.01). Likewise, multiple CD8+ expansions (two or more) were more common in MGUS/MM I patients than in MM II/III and controls (p < 0.01). The T cell expansions were stable over time in patients with a stable disease. A high degree of clonality of the expansions was detected by TCR CDR3 fragment length analysis, determination of Jβ gene usage and nucleotide sequencing. The frequent finding of oligoclonal CD8+ T cell expansions in patients with a low tumor mass, but not in patients with advanced disease justifies further work in order to identify the relevance of expanded CD8+ T cells. In one patient with T cell reactivity against the autologous myeloma idiotype, two expansions within the CD8 population (Vβ3 and Vβ5.2 respectively) displayed no reactivity against the idiotype. Instead, idiotype recognition was confined to a CD8 non-expanded Vβ22+ T cell population, with a highly restricted TCR usage (CDR3 fragment length analysis).

Original languageEnglish (US)
Pages (from-to)2245-2252
Number of pages8
JournalEuropean Journal of Immunology
Volume27
Issue number9
DOIs
StatePublished - Sep 1 1997

Keywords

  • Clonal expansion
  • Human
  • Immunotherapy
  • T cell receptor
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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