Linked Life Data

12653481

Source:http://linkedlifedata.com/resource/pubmed/id/12653481

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-3-25
pubmed:abstractText
Previously, we reported that the major stress-inducible heat shock protein 70 (Hsp70) acts as a recognition structure for natural killer (NK) cells, if localized on the cell surface of tumor cells. Incubation of purified NK cells with low-dose interleukin (IL)-2 (100 IU/mL) plus recombinant Hsp70-protein or the immunogenic 14-mer Hsp70-peptide TKDNNLLGRFELSG450-463, termed TKD (2 microg/mL), enhances the cytolytic activity against Hsp70 membrane-positive (CX+) but not against Hsp70-negative (CX-) tumor cells. Here, we show that the cytolytic activity against Hsp70-positive tumor cells is inducible by incubation of unseparated peripheral blood mononuclear cells (PBMNC) with low-dose IL-2 plus TKD. Cell sorting experiments revealed that within the PBMNC population CD94(+)/CD3(-) NK cells, and not CD94(-)/CD3(+) T cells, mediate the cytotoxic activity against Hsp70-positive tumor cells. The antitumoral effect of PBMNC stimulated either with IL-2 plus TKD or with IL-2 alone was assessed in tumor-bearing severe combined immunodeficiency/beige mice. A single intravenous (iv) injection of 40 x 10(6) IL-2 plus TKD-stimulated PBMNC (containing 5.2 x 10(6) NK cells) on day 4 results in a 60% reduction in tumor size, from 3.89 g to 1.56 g. In contrast, the adoptive transfer of the identical amount PBMNC stimulated with low-dose IL-2 only (containing 4.4 x 10(8) NK cells) reduces the tumor size only less than 10% (3.64 g). A phenotypic characterization of the excised tumors revealed that predominantly Hsp70-positive tumor cells were eliminated by TKD-activated PBMNC. Kinetic studies demonstrate that the in vivo cytolytic capacity of TKD-stimulated PBMNC is dependent on the effector to target cell ratio. An iv injection of effector cells on day 1 or 2 after tumor cell inoculation results in significantly smaller tumors (0.77 g or 0.89 g) on day 21 as compared with mice that were immunoreconstituted on day 4 or 8 (1.39 g or 2.23 g). The tumor size of nonimmunoreconstituted control animals was 3.55 g.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-10047535, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-10560910, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-10679071, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-10806214, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-10946262, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-11072250, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-11189449, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-11248808, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-11599573, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-1601523, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-2970594, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-4278109, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-7366733, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-7545313, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-7889575, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-8022479, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-8228242, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-8402925, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-8598315, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-8637592, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9126997, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9127634, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9311915, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9485212, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9586358, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9714069, http://linkedlifedata.com/resource/pubmed/commentcorrection/12653481-9834230
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1355-8145
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-73
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:12653481-Animals, pubmed-meshheading:12653481-Antigens, CD, pubmed-meshheading:12653481-Cell Division, pubmed-meshheading:12653481-Dose-Response Relationship, Drug, pubmed-meshheading:12653481-Female, pubmed-meshheading:12653481-HSP70 Heat-Shock Proteins, pubmed-meshheading:12653481-Humans, pubmed-meshheading:12653481-Interleukin-2, pubmed-meshheading:12653481-Killer Cells, Natural, pubmed-meshheading:12653481-Lectins, C-Type, pubmed-meshheading:12653481-Leukocytes, Mononuclear, pubmed-meshheading:12653481-Male, pubmed-meshheading:12653481-Mice, pubmed-meshheading:12653481-NK Cell Lectin-Like Receptor Subfamily D, pubmed-meshheading:12653481-Neoplasms, pubmed-meshheading:12653481-Peptide Fragments, pubmed-meshheading:12653481-Phenotype, pubmed-meshheading:12653481-Recombinant Fusion Proteins, pubmed-meshheading:12653481-Severe Combined Immunodeficiency, pubmed-meshheading:12653481-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Inhibition of tumor growth in mice with severe combined immunodeficiency is mediated by heat shock protein 70 (Hsp70)-peptide-activated, CD94 positive natural killer cells.
pubmed:affiliation
Department of Surgery, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93053 Regensburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't