Linked Life Data

1421393

Source:http://linkedlifedata.com/resource/pubmed/id/1421393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1992-12-7
pubmed:abstractText
We have studied the mechanisms underlying expansion of recombinant interleukin-2 (rIL-2)-stimulated natural killer (NK) cells in vitro. A population of NK cells expressing the CD56+/CD3-phenotype (98.9% +/- 0.42%) was obtained from normal human peripheral blood mononuclear cells (PBMNC) by fluorescence-activated cell sorting (FACS). Culture of NK cells in media containing rIL-2 (1,000 U/mL) for 18 days resulted in a population of activated NK cells (ANK) with significantly enhanced cytotoxicity, but only 2.6 +/- 0.56-fold expansion of cell number compared with the starting NK population. Culture of starting NK populations and autologous PBMNC in a Transwell system (Costar, Cambridge, MA), providing separation of the two cell populations by a 0.4-microns pore membrane, resulted in a dose-dependent increase in fold expansion of ANK (expansion = 19.9 +/- 4.0-fold; P < .001; n = 22) significantly greater than that observed when NK were cultured alone. Further experiments using the Transwell system showed that the stimulatory effect of autologous PBMNC on ANK progenitor proliferation resides in the CD14+ monocyte fraction (maximal expansion = 14.5 +/- 1.5-fold; n = 17) and not in the CD5+ T-lymphocyte or CD19+ B-lymphocyte fractions. Direct coculture of purified NK and autologous monocytes in the same compartment, thus permitting cell-cell contact, resulted in significantly greater expansion of the ANK population (30.6 +/- 4.7-fold expansion, P < .001; n = 10) than that observed when NK and monocytes were separated by the Transwell membrane. Finally, depletion of PBMNC of cells bearing CD5 and CD8 by panning on antibody-coated plastic flasks resulted in a starting cell population enriched for NK progenitors and for monocytes. Cultures of this resultant population for 18 days in the presence of rIL-2 yielded an ANK population similar to that obtained when CD56+/CD3- cells obtained by FACS were cocultured with autologous monocytes. These results suggest that proliferation of ANK requires autologous monocytes and is in part mediated by humoral factors, but is enhanced when NK and monocytes are in direct cell-cell contact. Depletion of cells bearing CD5 and CD8 from PBMNC is a single efficient method for obtaining a starting population capable of producing large numbers of ANK in culture that may lead to new therapeutic uses for the ANK population.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2221-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Role of monocytes in the expansion of human activated natural killer cells.
pubmed:affiliation
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't