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

Area of Science:

• Immunology
• Infectious Diseases
• Cytokine Biology

Background:

• Interleukin-27 (IL-27) is a cytokine in the IL-12 family, typically produced by innate immune cells.
• Regulatory T cells play a crucial role in modulating immune responses during infections.

Purpose of the Study:

• To identify and characterize novel regulatory CD4(+) T cells involved in malaria infection.
• To investigate the role of IL-27 produced by T cells in regulating immune responses during malaria.

Main Methods:

• Analysis of malaria-specific CD4(+) T cells.
• Detection of IL-27 production by T cells.
• Assessment of T cell proliferation and cytokine production (IL-2, IFN-γ).
• Studies in mice lacking IL-27 in T cells.

Main Results:

• A distinct population of Foxp3(-)CD11a(+)CD49d(+) regulatory CD4(+) T cells producing IL-27 was identified during malaria.
• These IL-27-producing T cells suppressed IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner.
• In mice lacking T cell-derived IL-27, IL-2 production and CD4(+) T cell expansion/IFN-γ production were enhanced, leading to reduced parasite burden.

Conclusions:

• A unique subset of IL-27-producing regulatory CD4(+) T cells actively suppresses anti-malarial T cell responses.
• Targeting these regulatory T cells or their IL-27 production could be a therapeutic strategy to enhance protective immunity against malaria.