Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-10-25
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1787-97
pubmed:dateRevised
2008-11-21
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
pubmed:year
1993
pubmed:articleTitle
Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells.
pubmed:affiliation
Divisione Universitaria di Ematologia, Ospedale Maggiore S. Giovanni Battista, Università di Torino, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't