Bystander T cells in human immune responses to dengue antigens
<p>Abstract</p> <p>Background</p> <p>Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs) and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-09-01
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| Series: | BMC Immunology |
| Online Access: | http://www.biomedcentral.com/1471-2172/11/47 |
| _version_ | 1819038018822995968 |
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| author | Suwannasaen Duangchan Romphruk Arunrat Leelayuwat Chanvit Lertmemongkolchai Ganjana |
| author_facet | Suwannasaen Duangchan Romphruk Arunrat Leelayuwat Chanvit Lertmemongkolchai Ganjana |
| author_sort | Suwannasaen Duangchan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs) and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen.</p> <p>Results</p> <p>Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ) induction in response to inactivated dengue serotype 2 antigen (Den2). The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA), which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK) (mean ± SE = 55.2 ± 3.3), CD4<sup>+</sup>T (24.5 ± 3.3) and CD8<sup>+</sup>T cells (17.9 ± 1.5), respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4<sup>+</sup>T = 26.9 ± 3.6% and CD8<sup>+</sup>T = 20.3 ± 2.1%) implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4<sup>+ </sup>and CD8<sup>+</sup>T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement.</p> <p>Conclusions</p> <p>This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.</p> |
| first_indexed | 2024-12-21T08:30:39Z |
| format | Article |
| id | doaj.art-3db020d3ba04490aa7542e8205b56b06 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-21T08:30:39Z |
| publishDate | 2010-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-3db020d3ba04490aa7542e8205b56b062022-12-21T19:10:13ZengBMCBMC Immunology1471-21722010-09-011114710.1186/1471-2172-11-47Bystander T cells in human immune responses to dengue antigensSuwannasaen DuangchanRomphruk ArunratLeelayuwat ChanvitLertmemongkolchai Ganjana<p>Abstract</p> <p>Background</p> <p>Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs) and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen.</p> <p>Results</p> <p>Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ) induction in response to inactivated dengue serotype 2 antigen (Den2). The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA), which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK) (mean ± SE = 55.2 ± 3.3), CD4<sup>+</sup>T (24.5 ± 3.3) and CD8<sup>+</sup>T cells (17.9 ± 1.5), respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4<sup>+</sup>T = 26.9 ± 3.6% and CD8<sup>+</sup>T = 20.3 ± 2.1%) implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4<sup>+ </sup>and CD8<sup>+</sup>T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement.</p> <p>Conclusions</p> <p>This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.</p>http://www.biomedcentral.com/1471-2172/11/47 |
| spellingShingle | Suwannasaen Duangchan Romphruk Arunrat Leelayuwat Chanvit Lertmemongkolchai Ganjana Bystander T cells in human immune responses to dengue antigens BMC Immunology |
| title | Bystander T cells in human immune responses to dengue antigens |
| title_full | Bystander T cells in human immune responses to dengue antigens |
| title_fullStr | Bystander T cells in human immune responses to dengue antigens |
| title_full_unstemmed | Bystander T cells in human immune responses to dengue antigens |
| title_short | Bystander T cells in human immune responses to dengue antigens |
| title_sort | bystander t cells in human immune responses to dengue antigens |
| url | http://www.biomedcentral.com/1471-2172/11/47 |
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