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

• Published in: Blood 1993-09, Vol.82 (6), p.1787-1797
• Main Authors: Massaia, M, Attisano, C, Peola, S, Montacchini, L, Omedé, P, Corradini, P, Ferrero, D, Boccadoro, M, Bianchi, A, Pileri, A
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal; Antigens, CD - immunology; Bone Marrow - immunology; Bone Marrow - pathology; CD3 Complex - immunology; Cells, Cultured; Flow Cytometry; Humans; Interferon-gamma - pharmacology; Kinetics; Lymphocyte Activation - drug effects; Lymphotoxin-alpha - pharmacology; Monocytes - immunology; Monocytes - pathology; Multiple Myeloma - blood; Multiple Myeloma - immunology; Multiple Myeloma - pathology; Muromonab-CD3 - immunology; Muromonab-CD3 - pharmacology; Neoplasm Staging; Plasma Cells - immunology; Recombinant Proteins - pharmacology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.6.1787.1787

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-gamma (P = .005) and tumor necrosis factor-beta (P = .001), but lower levels of tumor necrosis factor-alpha (P < .001) than normal individuals. Interferon-gamma 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.