Microglial activation milieu controls regulatory T cell responses

Area of Science:

• Neuroimmunology
• Innate Immunity
• T cell Regulation

Background:

• Mechanisms of brain inflammation and T cell activation are well-studied.
• Regulatory mechanisms of local innate immune cells in the brain are poorly understood.

Purpose of the Study:

• To investigate the regulatory properties of microglia, a key innate immune cell in the brain.
• To determine if microglia can induce regulatory T cells (Tregs) and influence immune responses in the central nervous system (CNS).

Main Methods:

• In vitro induction of Ag-specific CD4(+)Foxp3(+) regulatory T cells (Tregs) by microglia.
• Analysis of microglia's differential regulation of MHC class II, costimulatory molecules, and IL-10 based on IFN-γ and Ag dose.
• In vitro functional assays of microglia-induced Tregs inhibiting effector T cell proliferation.
• In vivo assessment of microglia-induced Tregs in attenuating experimental autoimmune encephalomyelitis (EAE).

Main Results:

• MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia were identified as potent inducers of Ag-specific CD4(+)Foxp3(+) Tregs in vitro.
• Microglia modulated MHC class II expression, costimulatory molecules, and IL-10 production in response to IFN-γ and Ag dose, directing either effector T cell or Treg induction.
• Microglia-induced Tregs demonstrated functional activity by inhibiting effector T cell proliferation in vitro.
• Adoptive transfer of microglia-induced Tregs attenuated the disease course of EAE in vivo.

Conclusions:

• MHC class II(+)CD40(dim)CD86(dim)IL-10(+) microglia possess regulatory properties.
• These microglia can induce functional Tregs that suppress immune responses.
• Microglia play a significant role in regulating local immune responses within the CNS.