+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Induction of antigen-specific CD8 T cells by monocyte-derived dendritic cells Influence of DC maturation on the recruited T cell repertoire

Induction of antigen-specific CD8 T cells by monocyte-derived dendritic cells Influence of DC maturation on the recruited T cell repertoire

Blood 98(11 Part 1): 510a, November 16

Dendritic cells (DC) are essential for the generation of primary adaptive immunity, and it is recognized that their modulation of T cell responses depends greatly on their stage of maturation and pattern of cytokines secreted. We used an in vitro model to assess the ability of immature and mature DC to induce antigen-specific CD8 T cells and compared the repertoire of the recruited T cells. Monocyte-derived DC differentiated with GM-CSF and IL-13 (Dendritophages(R), Dphi) were maturated with either the synthetic double-stranded RNA polyI:C+ anti-CD40 mAb, or with a bacterial extract (Ribomunyl), in presence or absence of IFNgamma. Addition of IFNgamma at the onset of maturation allowed higher secretion of IL-12 concomitant with lower secretion of IL-10. Kinetics studies showed that a contact as short as 3 h with maturation agents triggered an activation process that then proceeded and completed spontaneously. Most of IL-12 secretion occurred between 6 and 20 h from the initiation of maturation. Therefore, we analysed the function of Dphi that had been in contact with maturation agents for 3, 6, or 20 h. After maturation, Dphi were pulsed with a MelanA/MART1-derived peptide (26-35/27L) and used to stimulate autologous purified CD8 T cells. Using cytotoxicity assays, IFNgamma-ELISPOT, proliferation assays and tetramer staining, we found that only mature Dphi were able to generate and sustain antigen-specific CD8 T cells in absence of CD4 cells and exogenous cytokines. However, MelanA/MART1-specific CD8 cells could be induced by immature Dphi if exogenous cytokines (IL-12 and IL-6, IL-2 and IL-7) were added during stimulation. When Dphi maturation was triggered before the in vitro stimulation, a 6-h incubation in presence of Ribomunyl/INFgamma was optimal for the generation of CD8 responses, and mature Dphi were 80 to 400 times more potent than immature Dphi. Finally, the repertoire of the MelanA/MART1-specific T cells obtained was characterised by Immunoscope analysis. We found that, despite their dissimilar frequency, the CD8 generated were qualitatively similar. In the same individual, the MelanA/MART1-specific repertoires expanded by Dphi maturated by different agents were partially overlapping although in all cases very diverse. Overall, our results indicate that Dphi matured with Ribomunyl+IFNgamma are strong inducers of CD8 T cell responses and therefore constitute a useful tool for the development of future therapies against cancer.

(PDF emailed within 1 workday: $29.90)

Accession: 035125215

Download citation: RISBibTeXText

Related references

Activated plasmacytoid dendritic cells act synergistically with hepatitis B core antigen-pulsed monocyte-derived dendritic cells in the induction of hepatitis B virus-specific CD8 T-cell response. Clinical Immunology 129(2): 295-303, 2008

Monocyte-derived dendritic cells from HLA-matched allogeneic donors showed a greater ability to induce leukemic cell-specific T cells in comparison to leukemic cell-derived dendritic cells or monocyte-derived dendritic cells from AML patients. Leukemia Research 32(11): 1653-1660, 2008

Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses. Journal of Immunology 168(1): 197-206, 2001

Native Hiv-1 Tat Protein Targets Monocyte-Derived Dendritic Cells and Enhances Their Maturation, Function, and Antigen-Specific T Cell Responses. The Journal of Immunology 168(1): 197-206, 2002

Timing of antigen addition during maturation of monocyte-derived dendritic cells for antigen-specific proliferative response. Human Immunology 61(Suppl 1): S131, 2000

Rabbit antithymocyte globulin inhibits monocyte-derived dendritic cells maturation in vitro and polarizes monocyte-derived dendritic cells towards tolerogenic dendritic cells expressing indoleamine 2,3-dioxygenase. Transplantation 82(7): 965-974, 2006

Apoptotic dendritic cells induce tolerance in mice through suppression of dendritic cell maturation and induction of antigen-specific regulatory T cells. Journal of Immunology 183(11): 7104-7118, 2009

Generation of optimal monocyte-derived dendritic cells for immunotherapy Influence of maturation conditions on antigen presentation. Journal of Investigative Dermatology 117(4): 1008, 2001

Antigen-nonspecific T-cells mediate the maturation of immature monocyte-derived dendritic cells into interdigitating cells. Pathology International 50(Suppl.): A140, 2000

Human mesenchymal stem cells and renal tubular epithelial cells differentially influence monocyte-derived dendritic cell differentiation and maturation. Cellular Immunology 267(1): 30-38, 2011

Comparison of antigen specific immune responses induced by CMRF-44+ blood dendritic cells and monocyte derived dendritic cells. Blood 96(11 Part 2): 31b, November 16, 2000

Induction of a T helper cell response against the tumor-associated antigen HER2 using monocyte-derived dendritic cells. Cytotechnology 38(1-3): 155-164, 2008

Induction of antigen-specific cytotoxic T lymphocytes by recombinant HIV TAT-fusion protein-pulsed human monocyte-derived dendritic cells. Proceedings of the American Association for Cancer Research Annual Meeting 43: 677, 2002

Induction of antigen-specific CTL by recombinant HIV trans-activating fusion protein-pulsed human monocyte-derived dendritic cells. Journal of Immunology 170(3): 1291-1298, 2003

Generation of helper and cytotoxic CD4+T cell clones specific for the minor histocompatibility antigen H-Y, after in vitro priming of human T cells by HLA-identical monocyte-derived dendritic cells. Transplantation 71(10): 1449-1455, 2001