High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.
BACKGROUND:Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients...
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| Format: | Article |
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Public Library of Science (PLoS)
2007-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2092391?pdf=render |
| _version_ | 1818924542344560640 |
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| author | Tao Dong Edward Moran Nguyen Vinh Chau Cameron Simmons Kerstin Luhn Yanchun Peng Bridget Wills Nguyen Phuong Dung Le Thi Thu Thao Tran Tinh Hien Andrew McMichael Jeremy Farrar Sarah Rowland-Jones |
| author_facet | Tao Dong Edward Moran Nguyen Vinh Chau Cameron Simmons Kerstin Luhn Yanchun Peng Bridget Wills Nguyen Phuong Dung Le Thi Thu Thao Tran Tinh Hien Andrew McMichael Jeremy Farrar Sarah Rowland-Jones |
| author_sort | Tao Dong |
| collection | DOAJ |
| description | BACKGROUND:Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. METHODS AND FINDINGS:Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. CONCLUSION:Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease. |
| first_indexed | 2024-12-20T02:26:59Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:26:59Z |
| publishDate | 2007-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7b8bc352e94b4d1d875da226755331172022-12-21T19:56:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-12-01212e119210.1371/journal.pone.0001192High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.Tao DongEdward MoranNguyen Vinh ChauCameron SimmonsKerstin LuhnYanchun PengBridget WillsNguyen Phuong DungLe Thi Thu ThaoTran Tinh HienAndrew McMichaelJeremy FarrarSarah Rowland-JonesBACKGROUND:Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. METHODS AND FINDINGS:Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. CONCLUSION:Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease.http://europepmc.org/articles/PMC2092391?pdf=render |
| spellingShingle | Tao Dong Edward Moran Nguyen Vinh Chau Cameron Simmons Kerstin Luhn Yanchun Peng Bridget Wills Nguyen Phuong Dung Le Thi Thu Thao Tran Tinh Hien Andrew McMichael Jeremy Farrar Sarah Rowland-Jones High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. PLoS ONE |
| title | High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. |
| title_full | High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. |
| title_fullStr | High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. |
| title_full_unstemmed | High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. |
| title_short | High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. |
| title_sort | high pro inflammatory cytokine secretion and loss of high avidity cross reactive cytotoxic t cells during the course of secondary dengue virus infection |
| url | http://europepmc.org/articles/PMC2092391?pdf=render |
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