CD4+CD25+ regulatory T cells restrain pathogenic responses during Leishmania amazonensis infection

Jiaxiang Ji, Joseph Masterson, Jiaren Sun, Lynn Soong

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Although activation of CD4+ T cells mediates pathogenesis in Leishmania amazonensis (La)-infected mice, these susceptible mice do not develop a polarized Th2 response, suggesting a unique mechanism of disease susceptibility. To understand how Th cell activities are regulated, we examined the frequency and phenotypes of regulatory T (Treg) cells. At 1-3 wk of infection, relatively high percentages of CD4+CD25 +CD86+ T cells, as well as high levels of FoxP3, TGF-β1, and IL-10RI transcripts, were detected in the skin and draining lymph nodes, indicating local accumulation of Treg cells. Lesion-derived, IL-10-producing CD4+CD25+ cells effectively suppressed proliferation and cytokine (IL-2 and IFN-γ) production of CD4 +CD25- effector cells. Adoptive transfer of lesion-derived CD4+CD25+ cells to syngeneic, naive C57BL/6 mice before infection significantly reduced disease development. To farther validate the beneficial role of Treg cells in La infection, we adoptively transferred CD25+ T cell-depleted splenocytes (derived from naive mice) into RAG1-/- mice. This transfer rendered RAG1-/- mice more susceptible to La infection than the mice receiving control splenocytes. The beneficial effect of Treg cells was transitory and correlated with decreased activation of IFN-γ-producing effector T cells. This study uncovers an intriguing role of Treg cells in restraining pathogenic responses during nonhealing Leishmania infection and emphasizes a balance between Treg and Th1-like effector cells in determining the outcome of New World cutaneous leishmaniasis.

Original languageEnglish (US)
Pages (from-to)7147-7153
Number of pages7
JournalJournal of Immunology
Volume174
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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