Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells.
BACKGROUND: Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3144929?pdf=render |
| _version_ | 1818930512942596096 |
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| author | Nicole Bacher Edith Graulich Helmut Jonuleit Stephan Grabbe Kerstin Steinbrink |
| author_facet | Nicole Bacher Edith Graulich Helmut Jonuleit Stephan Grabbe Kerstin Steinbrink |
| author_sort | Nicole Bacher |
| collection | DOAJ |
| description | BACKGROUND: Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). METHODOLOGY/PRINCIPAL FINDINGS: IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an increased capacity of DC to stimulate T cell activation compared to control tolerogenic DC. We observed a strengthened T cell proliferation and increased IFN-γ production of CD4(+) and CD8(+) T cells stimulated by IFN-α-DC, demonstrating a restoration of the immunogenic capacity of tolerogenic DC in the presence of IFN-α. Notably, restimulation experiments revealed that IFN-α treatment of tolerogenic DC abolished the induction of T cell anergy and suppressor function of iTregs. In contrast, IFN-α neither affected the priming of iTregs nor converted iTregs into effector T cells. CONCLUSIONS/SIGNIFICANCE: IFN-α inhibits the induction of T cell tolerance by reversing the tolerogenic function of human DC. |
| first_indexed | 2024-12-20T04:01:53Z |
| format | Article |
| id | doaj.art-0fddd41d2d294cb996401f82df39a34c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T04:01:53Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0fddd41d2d294cb996401f82df39a34c2022-12-21T19:54:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2276310.1371/journal.pone.0022763Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells.Nicole BacherEdith GraulichHelmut JonuleitStephan GrabbeKerstin SteinbrinkBACKGROUND: Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). METHODOLOGY/PRINCIPAL FINDINGS: IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an increased capacity of DC to stimulate T cell activation compared to control tolerogenic DC. We observed a strengthened T cell proliferation and increased IFN-γ production of CD4(+) and CD8(+) T cells stimulated by IFN-α-DC, demonstrating a restoration of the immunogenic capacity of tolerogenic DC in the presence of IFN-α. Notably, restimulation experiments revealed that IFN-α treatment of tolerogenic DC abolished the induction of T cell anergy and suppressor function of iTregs. In contrast, IFN-α neither affected the priming of iTregs nor converted iTregs into effector T cells. CONCLUSIONS/SIGNIFICANCE: IFN-α inhibits the induction of T cell tolerance by reversing the tolerogenic function of human DC.http://europepmc.org/articles/PMC3144929?pdf=render |
| spellingShingle | Nicole Bacher Edith Graulich Helmut Jonuleit Stephan Grabbe Kerstin Steinbrink Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. PLoS ONE |
| title | Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. |
| title_full | Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. |
| title_fullStr | Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. |
| title_full_unstemmed | Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. |
| title_short | Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells. |
| title_sort | interferon α abrogates tolerance induction by human tolerogenic dendritic cells |
| url | http://europepmc.org/articles/PMC3144929?pdf=render |
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