Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection

Immunity. 2016 Mar 15;44(3):672-682. doi: 10.1016/j.immuni.2016.02.011. Epub 2016 Mar 8.

Abstract

Interleukin-27 (IL-27) is a heterodimeric regulatory cytokine of the IL-12 family, which is produced by macrophages, dendritic cells, and B cells upon stimulation through innate immune receptors. Here, we described regulatory CD4(+) T cells that produce IL-27 in response to T cell receptor stimulation during malaria infection, inhibiting IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner. IL-27-producing CD4(+) T cells were Foxp3(-)CD11a(+)CD49d(+) malaria antigen-specific CD4(+) T cells and were distinct from interferon-γ (IFN-γ) producing Th1 or IL-10 producing Tr1 cells. In mice lacking IL-27 in T cells, IL-2 production was restored and clonal expansion and IFN-γ production by specific CD4(+) T cells were improved, culminating in reduced parasite burden. This study highlights a unique population of IL-27 producing regulatory CD4(+) T cells and their critical role in the regulation of the protective immune response against malaria parasites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / parasitology
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunity, Innate
  • Interleukin-27 / genetics
  • Interleukin-27 / metabolism*
  • Malaria / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmodium berghei / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Receptors, Interleukin
  • T-Lymphocytes, Regulatory / parasitology
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Cytokines
  • Il27ra protein, mouse
  • Interleukin-27
  • Receptors, Antigen, T-Cell
  • Receptors, Cytokine
  • Receptors, Interleukin