At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells

J Immunol. 2010 May 1;184(9):5375-82. doi: 10.4049/jimmunol.0904067. Epub 2010 Mar 31.

Abstract

Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil(+), as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil(+) compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10-producing aTreg/Tr1s in Fil(+). Together, these data show that at steady state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Cytokines / biosynthesis
  • Elephantiasis, Filarial / immunology*
  • Enterobiasis / immunology
  • Enterobius / immunology
  • Homeostasis / immunology*
  • Humans
  • Hymenolepiasis / immunology
  • Hymenolepis nana / immunology
  • Mansonella / immunology
  • Mansonelliasis / immunology*
  • Microfilariae / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / parasitology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / parasitology
  • Wuchereria bancrofti / immunology

Substances

  • Cytokines