Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhance...

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Autore principale: Simmons, Cameron
Natura: Journal Article
Lingua:inglese
Pubblicazione: 2018
Accesso online:https://demo7.dspace.org/handle/123456789/131
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
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description Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.
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spelling oai:localhost:123456789-1312021-04-07T16:30:08Z Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection Simmons, Cameron Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease. 2018-09-14T11:14:57Z 2017-07-05T05:48:16Z 2018-09-14T11:14:57Z 2007-05-14 Journal Article https://demo7.dspace.org/handle/123456789/131 English
spellingShingle Simmons, Cameron
Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title_full Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title_fullStr Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title_full_unstemmed Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title_short Increased frequencies of CD4(+) CD25(high) regulatory T cells in acute dengue infection
title_sort increased frequencies of cd4 cd25 high regulatory t cells in acute dengue infection
url https://demo7.dspace.org/handle/123456789/131
work_keys_str_mv AT simmonscameron increasedfrequenciesofcd4cd25highregulatorytcellsinacutedengueinfection