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Measles virus infection in adults induces production of IL-10 and is associated with increased CD4+ CD25+ regulatory T cells

J Immunol. 2008 Nov 15;181(10):7356-66. doi: 10.4049/jimmunol.181.10.7356.

Abstract

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(+)CD127(low) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis*
  • Interleukin-2 / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Measles / immunology*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antibodies, Viral
  • Interleukin-2
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • Interleukin-10
  • Interferon-gamma