CD4+ CD25+ Foxp3- T-regulatory cells produce both gamma interferon and interleukin-10 during acute severe murine spotted fever rickettsiosis

Rong Fang, Nahed Ismail, Thomas Shelite, David H. Walker

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Spotted fever group rickettsiae cause life-threatening human infections worldwide. Until now, the immune regulatory mechanisms involved in fatal rickettsial infection have been unknown. C3H/HeN mice infected with 3 × 105 PFU of Rickettsia conorii developed an acute progressive disease, and all mice succumbed to this infection. A sublethal infection induced protective immunity, and mice survived. Compared to splenic T cells from sublethally infected mice, splenic T cells from lethally infected mice produced significantly lower levels of interleukin-2 (IL-2) and gamma interferon (IFN-γ) and a higher level of IL-10, but not of IL-4 or transforming growth factor β, and there was markedly suppressed CD4+ T-cell proliferation in response to antigen-specific stimulation with R. conorii. Furthermore, lethal infection induced significant expansion of CD4+ CD25+ Foxp3- T cells in infected organs compared to the levels in naïve and sublethally infected mice. In a lethal infection, splenic CD4+ CD25+ Foxp3- T cells, which were CTLA-4high T-bet+ and secreted both IFN-γ and IL-10, suppressed the proliferation of and IL-2 production by splenic CD4+ CD25- Foxp3- T cells in vitro. Interestingly, depletion of CD25+ T cells in vivo did not change the disease progression, but it increased the bacterial load in the lung and liver, significantly reduced the number of IFN-γ-producing Th1 cells in the spleen, and increased the serum levels of IFN-γ. These results suggested that CD4+ CD25 + T cells generated in acute murine spotted fever rickettsiosis are Th1-cell-related adaptive T-regulatory cells, which substantially contribute to suppressing the systemic immune response, possibly by a mechanism involving IL-10 and/or cytotoxic T-lymphocyte antigen 4.

Original languageEnglish (US)
Pages (from-to)3838-3849
Number of pages12
JournalInfection and immunity
Issue number9
StatePublished - Sep 2009

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


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