The Journal of Experimental Medicine
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Published online April 23, 2007
doi:10.1084/jem.20061381
The Journal of Experimental Medicine, Vol. 204, No. 5, 979-985
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Lühn et al.
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BRIEF DEFINITIVE REPORT

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

Kerstin Lühn1, Cameron P. Simmons2, Edward Moran1, Nguyen Thi Phuong Dung2, Tran Nguyen Bich Chau2, Nguyen Than Ha Quyen2, Le Thi Thu Thao3, Tran Van Ngoc3, Nguyen Minh Dung3, Bridget Wills2, Jeremy Farrar2, Andrew J. McMichael1, Tao Dong1, and Sarah Rowland-Jones1

1 Weatherall Institute of Molecular Medicine, Medical Reasearch Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
2 Oxford University Clinical Research Unit and 3 The Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam

CORRESPONDENCE Kerstin Lühn: kerstin.luhn{at}imm.ox.ac.uk

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.

T. Dong and S. Rowland-Jones contributed equally to this paper.


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