Oxidative stress promotes polarization of human T cell differentiation toward a T helper 2 phenotype

Miranda R. King, Anisa S. Ismail, Laurie S. Davis, David R. Karp

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

These studies were conducted to determine the effects of oxidative stress on human T cell differentiation and polarization into Th1 or Th2 phenotypes. Highly purified naive CD4+ T cells were isolated from PBMC of healthy, nonatopic donors. CD4+ T cells were stimulated with anti-CD3 and anti-CD28 mAb in the presence or absence of oxidative stress as supplied by 2,3-dimethoxy-1,4-naplithoquinone (DMNQ), which generates a low level of superoxide anion. Increases in cellular superoxide were observed by exposure to DMNQ. Exposure of unpolarized CD4+ T cells to IL-12 or IL-4 resulted in a Th1 or Th2 phenotype, respectively. T cells stimulated in the absence of polarizing cytokines secreted modest amounts of IFN-γ and TNF-α. Cells stimulated in the continuous presence of 5 μM DMNQ, displayed a marked up-regolation in Th2 cytokines, including IL-4, IL-5, and IL-13, but not the Th1 cytokine IFN-γ. Th2 responses were blunted by concomitant exposure to thiol antioxidants. Long-term exposure of T cells to DMNQ resulted in growth of cells expressing CCR4, and a decrease in cells expressing CXCR3, indicating phenotypic conversion to Th2 cells. These results suggest that oxidative stress favors a Th2-polarizing condition.

Original languageEnglish (US)
Pages (from-to)2765-2772
Number of pages8
JournalJournal of Immunology
Volume176
Issue number5
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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