Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells

Massimo Massaia, Carmela Attisano, Silvia Peola, Laura Montacchini, Paola Omedé, Paolo Corradini, Dario Ferrero, Mario Boccadoro, Alberto Bianchi, Alessandro Pileri

Research output: Contribution to journalArticle

Abstract

We have recently shown that peripheral blood T cells of multiple myeloma (MM) patients are very susceptible to stimulation of the T-cell receptor/CD3 complex with anti-CD3 monoclonal antibodies (MoAbs). CD3 stimulation is currently under clinical investigation as a nonspecific approach to boost antitumor effector mechanisms. The aim of this study was to determine whether the hyperreactivity of MM T cells to CD3 stimulation could be exploited to generate antitumor activity. Bone marrow mononuclear cells (BMMCs) from 65 MM patients were stimulated with the anti-CD3 MoAb OKT3 and the effect of this stimulation on autologous T cells and plasma cells was evaluated. The number of CD3+ CD25+ cells on day 6 was significantly higher in MM than the controls (30 normal individuals) (P = .001). Kinetic studies showed that 3H-thymidine incorporation peaked on day 3 and that the T-cell expansion peaked on days 5 and 6. In MM, T-cell activation markedly affected the survival of autologous plasma cells; their number in OKT3-treated cultures was significantly lower than in unstimulated cultures (P <.0001). T-cell activation and plasma cell decrease were not observed when T cells were removed from BMMC preparations. MM produced significantly higher levels of interferon-γ (P = .005) and tumor necrosis factor-β (P = .001), but lower levels of tumor necrosis factor-α (P <.001) than normal individuals. Interferon-γ only was partially involved in CD3-induced plasma cell killing. Transwell cultures showed that the main mechanism by which CD3+ CD25+ cells affected plasma cells was direct cell-to-cell contact rather than cytokines. In conclusion, T cells in MM BMMCs possess distinct features in terms of susceptibility to CD3 stimulation and cytokine production compared with normal bone marrow T cells that can be exploited to generate antiplasma cell activity.

Original languageEnglish
Pages (from-to)1787-1797
Number of pages11
JournalBlood
Volume82
Issue number6
Publication statusPublished - Sep 15 1993

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells'. Together they form a unique fingerprint.

  • Cite this

    Massaia, M., Attisano, C., Peola, S., Montacchini, L., Omedé, P., Corradini, P., Ferrero, D., Boccadoro, M., Bianchi, A., & Pileri, A. (1993). Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells. Blood, 82(6), 1787-1797.