DNA threads released by activated CD4⁺ T lymphocytes provide autocrine costimulation

Area of Science:

• Immunology
• Cell Biology
• Neuroscience

Background:

• DNA traps are involved in innate immunity.
• CD4+ T cells regulate adaptive immunity.
• Extracellular DNA can mediate immune responses.

Purpose of the Study:

• To investigate the role of CD4+ T cells in releasing extracellular DNA.
• To determine the signaling function of these DNA extrusions.
• To explore the therapeutic potential of targeting this mechanism in autoimmune diseases.

Main Methods:

• Detection of extracellular DNA threads from activated CD4+ T cells.
• Pharmacologic inhibition of mitochondrial reactive oxygen species (mtROS).
• Assessment of T cell priming and cytokine production in vitro.
• Evaluation of disease severity in a mouse model of multiple sclerosis (EAE).

Main Results:

• Activated CD4+ T cells extrude DNA threads that provide autocrine costimulatory signals.
• Mitochondrial ROS are essential for DNA extrusion by CD4+ T cells.
• Inhibition of mtROS reduces T cell priming and ameliorates EAE disease severity.
• Extracellular DNA threads are found in lymph nodes during EAE.

Conclusions:

• Activated T helper cells release DNA threads for intrinsic immune costimulation.
• mtROS blockade is a potential therapeutic strategy for CD4+ T cell-mediated autoimmune disorders.
• This mechanism is relevant to diseases like multiple sclerosis and neuromyelitis optica.