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The Journal of Immunology, 2008, 181, 7356 -7366
Copyright © 2008 by The American Association of Immunologists, Inc.

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Measles Virus Infection in Adults Induces Production of IL-10 and Is Associated with Increased CD4+CD25+ Regulatory T Cells1

Xue-lian Yu2,*,{dagger}, Yu-ming Cheng*,{dagger}, Bi-sheng Shi*,{dagger}, Fang-xing Qian§, Feng-bin Wang*, Xi-nian Liu*, Hai-ying Yang*, Qing-nian Xu*, Tang-kai Qi*, Li-jun Zha*, Zheng-hong Yuan3,*,{dagger} and Reena Ghildyal3,4,*,{ddagger}

* Scientific Research Unit, Shanghai Public Health Clinical Center, and {dagger} Ministry of Education and Health Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China; {ddagger} Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia; and § Changning Hospital, Shanghai, China

Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-{alpha} mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-{gamma} were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4+ and CD8+ T cells in patient PBMC. Interestingly, we found that CD4+CD25+CD127low regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14+ and CD4+CD25+ cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by a grant from the Fudan University Youth Research Foundation, Shanghai, China, and the Shanghai Public Health Center Research Fund.

2 Current address: Shanghai Municipal Center for Disease Control and Prevention; 1380 Zhongshan West Road, Shanghai, China.

3 Z.-h.Y. and R.G. share senior authorship.

4 Address correspondence and reprint requests to Dr. Reena Ghildyal, Department of Biochemistry and Molecular Biology, Monash University, Wellington Parade, Clayton 3800, Victoria, Australia. E-mail address: Reena.Ghildyal{at}med.monash.edu.au

5 Abbreviations used in this paper: MV, measles virus; MOI, multiplicity of infection; CBA, cytometric bead array; Treg, regulatory T cell; IQR, interquartile range.




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