Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB.
Dendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF-kappaB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the eff...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797053920294469632 |
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| author | Calder, V Bondeson, J Brennan, F Foxwell, B Feldmann, M |
| author_facet | Calder, V Bondeson, J Brennan, F Foxwell, B Feldmann, M |
| author_sort | Calder, V |
| collection | OXFORD |
| description | Dendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF-kappaB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF-kappaB in DCs during presentation of antigen to memory T cells in vitro. Peripheral blood monocytes were differentiated into immature DCs with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor, and pulsed with an immunogenic tetanus toxoid peptide. Upon maturation, the antigen-pulsed DCs were highly effective in presenting antigen to autologous T cells. However, stimulation with antigen-pulsed DCs overexpressing IotakappaBetaalpha, the endogenous inhibitor of NF-kappaB, led to a significant reduction in T-cell proliferation, and decreased production of interferon-gamma, IL-4 and IL-10, whereas transforming growth factor-beta production was low throughout. There was a significant increase in apoptosis of antigen-specific T cells, even in the presence of IL-2, which was not found in resting T cells. Similar findings were observed using a proteasome inhibitor to block NF-kappaB. The effective downregulation of antigen-specific T-cell responses following blockade of NF-kappaB in DCs could be a useful approach for immunomodulating inflammatory T-cell responses. |
| first_indexed | 2024-03-06T18:50:19Z |
| format | Journal article |
| id | oxford-uuid:10018282-f7a1-4c69-ab00-85ddf49c278b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:50:19Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:10018282-f7a1-4c69-ab00-85ddf49c278b2022-03-26T09:54:07ZAntigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:10018282-f7a1-4c69-ab00-85ddf49c278bEnglishSymplectic Elements at Oxford2003Calder, VBondeson, JBrennan, FFoxwell, BFeldmann, MDendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF-kappaB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF-kappaB in DCs during presentation of antigen to memory T cells in vitro. Peripheral blood monocytes were differentiated into immature DCs with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor, and pulsed with an immunogenic tetanus toxoid peptide. Upon maturation, the antigen-pulsed DCs were highly effective in presenting antigen to autologous T cells. However, stimulation with antigen-pulsed DCs overexpressing IotakappaBetaalpha, the endogenous inhibitor of NF-kappaB, led to a significant reduction in T-cell proliferation, and decreased production of interferon-gamma, IL-4 and IL-10, whereas transforming growth factor-beta production was low throughout. There was a significant increase in apoptosis of antigen-specific T cells, even in the presence of IL-2, which was not found in resting T cells. Similar findings were observed using a proteasome inhibitor to block NF-kappaB. The effective downregulation of antigen-specific T-cell responses following blockade of NF-kappaB in DCs could be a useful approach for immunomodulating inflammatory T-cell responses. |
| spellingShingle | Calder, V Bondeson, J Brennan, F Foxwell, B Feldmann, M Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title | Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title_full | Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title_fullStr | Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title_full_unstemmed | Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title_short | Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaB. |
| title_sort | antigen specific t cell downregulation by human dendritic cells following blockade of nf kappab |
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