PMID- 11071646
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 10
DP  - 2000 Nov 15
TI  - Efficient priming of protein antigen-specific human CD4(+) T cells by 
      monocyte-derived dendritic cells.
PG  - 3490-8
AB  - 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.
FAU - Schlienger, K
AU  - Schlienger K
AD  - Department of Molecular and Cellular Engineering, University of Pennsylvania, 
      Philadelphia, USA.
FAU - Craighead, N
AU  - Craighead N
FAU - Lee, K P
AU  - Lee KP
FAU - Levine, B L
AU  - Levine BL
FAU - June, C H
AU  - June CH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens)
RN  - 0 (Tetanus Toxin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
RN  - 9013-72-3 (Hemocyanins)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Adjuvants, Immunologic/biosynthesis
MH  - Antigen Presentation/*immunology
MH  - Antigen-Presenting Cells/cytology/immunology
MH  - Antigens/immunology/pharmacology
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - CD40 Ligand/pharmacology
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Lineage/immunology
MH  - Dendritic Cells/cytology/*immunology
MH  - Hemocyanins/immunology/pharmacology
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin-12/biosynthesis
MH  - Leukocyte Common Antigens/drug effects/immunology/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Monocytes/cytology
MH  - Tetanus Toxin/immunology/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
AID - S0006-4971(20)48289-8 [pii]
PST - ppublish
SO  - Blood. 2000 Nov 15;96(10):3490-8.