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" |
