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

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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

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T-cells
Bone
Multiple Myeloma
Bone Marrow
T-Lymphocytes
Plasma Cells
Bone Marrow Cells
Plasmas
Muromonab-CD3
Cell culture
Interferons
Tumor Necrosis Factor-alpha
Chemical activation
CD3 Antigens
Cytokines
T-Cell Antigen Receptor
Thymidine
Blood Cells
Blood
Monoclonal Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

Massaia, M., Attisano, C., Peola, S., Montacchini, L., Omedé, P., Corradini, P., ... 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.

Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells. / Massaia, Massimo; Attisano, Carmela; Peola, Silvia; Montacchini, Laura; Omedé, Paola; Corradini, Paolo; Ferrero, Dario; Boccadoro, Mario; Bianchi, Alberto; Pileri, Alessandro.

In: Blood, Vol. 82, No. 6, 15.09.1993, p. 1787-1797.

Research output: Contribution to journalArticle

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, vol. 82, no. 6, pp. 1787-1797.
Massaia M, Attisano C, Peola S, Montacchini L, Omedé P, Corradini P et al. Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells. Blood. 1993 Sep 15;82(6):1787-1797.
Massaia, Massimo ; Attisano, Carmela ; Peola, Silvia ; Montacchini, Laura ; Omedé, Paola ; Corradini, Paolo ; Ferrero, Dario ; Boccadoro, Mario ; Bianchi, Alberto ; Pileri, Alessandro. / Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells. In: Blood. 1993 ; Vol. 82, No. 6. pp. 1787-1797.
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