Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

Kerstin Lühn, Cameron P. Simmons, Edward Moran, Nguyen Thi Phuong Dung, Tran Nguyen Bich Chau, Nguyen Than Ha Quyen, Le Thi Thu Thao, Tran Van Ngoc, Minh Dung Nguyen, Bridget Wills, Jeremy Farrar, Andrew J. McMichael, Tao Dong, Sarah Rowland-Jones

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 +CD25highFoxP3+ 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. JEM

Original languageEnglish
Pages (from-to)979-985
Number of pages7
JournalJournal of Experimental Medicine
Volume204
Issue number5
DOIs
Publication statusPublished - 1 May 2007

Cite this

Lühn, K., Simmons, C. P., Moran, E., Dung, N. T. P., Chau, T. N. B., Quyen, N. T. H., ... Rowland-Jones, S. (2007). Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection. Journal of Experimental Medicine, 204(5), 979-985. https://doi.org/10.1084/jem.20061381
Lühn, Kerstin ; Simmons, Cameron P. ; Moran, Edward ; Dung, Nguyen Thi Phuong ; Chau, Tran Nguyen Bich ; Quyen, Nguyen Than Ha ; Thao, Le Thi Thu ; Van Ngoc, Tran ; Nguyen, Minh Dung ; Wills, Bridget ; Farrar, Jeremy ; McMichael, Andrew J. ; Dong, Tao ; Rowland-Jones, Sarah. / Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 5. pp. 979-985.
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abstract = "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 +CD25highFoxP3+ 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. JEM",
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Lühn, K, Simmons, CP, Moran, E, Dung, NTP, Chau, TNB, Quyen, NTH, Thao, LTT, Van Ngoc, T, Nguyen, MD, Wills, B, Farrar, J, McMichael, AJ, Dong, T & Rowland-Jones, S 2007, 'Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection' Journal of Experimental Medicine, vol. 204, no. 5, pp. 979-985. https://doi.org/10.1084/jem.20061381

Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection. / Lühn, Kerstin; Simmons, Cameron P.; Moran, Edward; Dung, Nguyen Thi Phuong; Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thao, Le Thi Thu; Van Ngoc, Tran; Nguyen, Minh Dung; Wills, Bridget; Farrar, Jeremy; McMichael, Andrew J.; Dong, Tao; Rowland-Jones, Sarah.

In: Journal of Experimental Medicine, Vol. 204, No. 5, 01.05.2007, p. 979-985.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lühn, Kerstin

AU - Simmons, Cameron P.

AU - Moran, Edward

AU - Dung, Nguyen Thi Phuong

AU - Chau, Tran Nguyen Bich

AU - Quyen, Nguyen Than Ha

AU - Thao, Le Thi Thu

AU - Van Ngoc, Tran

AU - Nguyen, Minh Dung

AU - Wills, Bridget

AU - Farrar, Jeremy

AU - McMichael, Andrew J.

AU - Dong, Tao

AU - Rowland-Jones, Sarah

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AB - 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 +CD25highFoxP3+ 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. JEM

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