Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-11-27
pubmed:abstractText
Dendritic cells (DCs) have the unique ability to initiate an immune response in vivo by capturing antigens (Ags) in peripheral tissues and migrating to secondary lymphoid organs, where they sensitize naive CD4(+) T cells. To mimic this process in vitro, previous studies have shown that DCs directly isolated from peripheral blood can be used to elicit primary responses to neoantigens (neoAgs). In other studies, when monocyte-derived DCs have been utilized to sensitize total CD4(+) T cells in vitro, only secondary proliferation to neoAgs could be elicited. In the present study, the relative abilities of CD40 ligation, protein kinase C activation, and culture in tumor necrosis factor alpha (TNF-alpha) to induce functional and phenotypic maturation of human DCs from monocyte precursors were compared. Optimal TNF-alpha-induced maturation of DCs required a prolonged 4-day culture. It was then found that loading immature DCs with the neoAgs keyhole limpet hemocyanin or human immunodeficiency virus-1 p24 gag prior to TNF-alpha-induced maturation, rather than after maturation, was crucial to sensitize CD4(+) T cells to new Ags. This primary proliferation to neoAgs was initiated from the CD4(+) CD45RA(+) naive T-cell population. Finally, it was found that monocyte-derived DCs acquired the ability to secrete interleukin-12 p70, after contact with Ag-specific T cells. The ability to prime and expand Ag-specific CD4(+) T cells ex vivo to neoAgs in serum-free conditions has potential application for cellular vaccination and adoptive immunotherapy.
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
15
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3490-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11071646-Adjuvants, Immunologic, pubmed-meshheading:11071646-Antigen Presentation, pubmed-meshheading:11071646-Antigen-Presenting Cells, pubmed-meshheading:11071646-Antigens, pubmed-meshheading:11071646-Antigens, CD45, pubmed-meshheading:11071646-CD4-Positive T-Lymphocytes, pubmed-meshheading:11071646-CD40 Ligand, pubmed-meshheading:11071646-Cell Culture Techniques, pubmed-meshheading:11071646-Cell Differentiation, pubmed-meshheading:11071646-Cell Lineage, pubmed-meshheading:11071646-Dendritic Cells, pubmed-meshheading:11071646-Hemocyanin, pubmed-meshheading:11071646-Humans, pubmed-meshheading:11071646-Immunophenotyping, pubmed-meshheading:11071646-Interleukin-12, pubmed-meshheading:11071646-Lymphocyte Activation, pubmed-meshheading:11071646-Monocytes, pubmed-meshheading:11071646-Tetanus Toxin, pubmed-meshheading:11071646-Tetradecanoylphorbol Acetate, pubmed-meshheading:11071646-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Efficient priming of protein antigen-specific human CD4(+) T cells by monocyte-derived dendritic cells.
pubmed:affiliation
Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S.