Langerhans-type dendritic cells genetically modified to express full-length antigen optimally stimulate CTLs in a CD4-dependent manner Journal Article


Authors: Yuan, J.; Latouche, J. B.; Hodges, J.; Houghton, A. N.; Heller, G.; Sadelain, M.; Riviere, I.; Young, J. W.
Article Title: Langerhans-type dendritic cells genetically modified to express full-length antigen optimally stimulate CTLs in a CD4-dependent manner
Abstract: Oncoretroviral vectors encoding either full-length Ag or a corresponding immunodominant peptide were expressed in Langerhans-type dendritic cells (LCs) differentiated from CD34+ progenitors. We used human CMV as a model Ag restricted by HLA-A*0201 to define parameters for eventual expression of cancer Ags by LCs for active immunization against tumors. Stimulation by CMVpp65495-503-pulsed LCs, CMVpp65495-503-transduced LCs, and full-length CMVpp65-transduced LCs respectively increased tetramer-reactive T cells with an effector memory phenotype by 10 ± 11, 34 ± 21, and 51 ± 24-fold (p < 0.05) from CMV-seropositive donors. CMV-specific CD8+ CTLs achieved respective frequencies of 231 ± 102, 583 ± 219, and 714 ± 281 spot-forming cells per 105 input cells (p < 0.01) in ELISPOT assays for IFN-γ secretion. LCs expressing full-length Ag stimulated greater lytic activity than either peptide-transduced or peptide-pulsed LCs (p < 0.05), all in the absence of exogenous cytokines. pp65-transduced LCs presenting class I and II MHC-restricted epitopes expanded IFN-γ-secreting CD4+ T cells, whereas pp65495-503- transduced LCs did not. CD4+ T cell numbers even declined after stimulation by pp65495-503 peptide-pulsed LCs. CD4+ T cell depletion confirmed their contribution to the more robust CTL responses. LCs, transduced with a retroviral vector encoding full-length Ag, stimulate potent CTLs directed against multiple epitopes in a CD4+ Th cell-dependent manner. Copyright © 2006 by The American Association of Immunologists, Inc.
Keywords: controlled study; human cell; flow cytometry; antigen expression; phenotype; cells, cultured; cd34 antigen; dendritic cell; protein binding; cell differentiation; genetic transduction; dna modification; gamma interferon; genetic engineering; cd4+ t lymphocyte; cd4-positive t-lymphocytes; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; retrovirus vector; transgene; phosphoproteins; stem cells; immunostimulation; hematopoietic stem cell; enzyme linked immunospot assay; memory cell; hla a antigen; antigens, cd4; antigens, cd34; cytomegalovirus antigen pp65; cytomegalovirus; hla-a antigens; viral matrix proteins; lymphocyte depletion; transgenes; immunologic memory; retroviridae; major histocompatibility antigen class 1; major histocompatibility complex restriction; langerhans cell; langerhans cells; active immunization; interferon type ii; interferon production
Journal Title: Journal of Immunology
Volume: 176
Issue: 4
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2006-02-15
Start Page: 2357
End Page: 2365
Language: English
PUBMED: 16455993
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 6" - "Export Date: 4 June 2012" - "CODEN: JOIMA" - "Source: Scopus"