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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1993-10-25
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphotoxin-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Muromonab-CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1787-97
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:8400233-Antibodies, Monoclonal,
pubmed-meshheading:8400233-Antigens, CD,
pubmed-meshheading:8400233-Antigens, CD3,
pubmed-meshheading:8400233-Bone Marrow,
pubmed-meshheading:8400233-Cells, Cultured,
pubmed-meshheading:8400233-Flow Cytometry,
pubmed-meshheading:8400233-Humans,
pubmed-meshheading:8400233-Interferon-gamma,
pubmed-meshheading:8400233-Kinetics,
pubmed-meshheading:8400233-Lymphocyte Activation,
pubmed-meshheading:8400233-Lymphotoxin-alpha,
pubmed-meshheading:8400233-Monocytes,
pubmed-meshheading:8400233-Multiple Myeloma,
pubmed-meshheading:8400233-Muromonab-CD3,
pubmed-meshheading:8400233-Neoplasm Staging,
pubmed-meshheading:8400233-Plasma Cells,
pubmed-meshheading:8400233-Recombinant Proteins,
pubmed-meshheading:8400233-T-Lymphocyte Subsets,
pubmed-meshheading:8400233-T-Lymphocytes
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pubmed:year |
1993
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pubmed:articleTitle |
Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells.
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pubmed:affiliation |
Divisione Universitaria di Ematologia, Ospedale Maggiore S. Giovanni Battista, Università di Torino, Italy.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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