Activated Mesenchymal Stromal Cells Process and Present Antigens Regulating Adaptive Immunity

Area of Science:

• Immunology
• Cell Biology
• Translational Medicine

Background:

• Mesenchymal stromal cells (MSCs) possess inherent immunomodulatory properties.
• Their potential for inducing antigen-specific immune regulation requires further investigation.

Purpose of the Study:

• To determine if activated MSCs can induce antigen-specific immune regulation.
• To analyze the phenotype, immunosuppressive capacity, and metabolic activity of interferon-γ-activated MSCs.
• To assess the ability of activated MSCs pulsed with islet auto-antigen (GAD65) to modulate adaptive immunity.

Main Methods:

• Bone marrow-derived human MSCs were activated with interferon-γ.
• Phenotypic analysis included HLA class II, PD-L1, IDO, and CD86 expression.
• Antigen uptake, processing, and metabolic activity (glycolysis, mitochondrial respiration) were assessed.
• GAD65-specific T-cells were stimulated with MSCs pulsed with GAD65 peptide.

Main Results:

• Inflammatory activation increased HLA class II, PD-L1, and intracellular IDO expression on MSCs, while CD86 remained absent.
• MSC metabolic phenotype (glycolysis, mitochondrial respiration) was unchanged upon activation.
• Activated MSCs pulsed with GAD65 peptide inhibited proliferation of GAD65-specific T-cells without inducing alloreactivity.
• MSC conditioning prevented T-cell proliferation upon subsequent activation by dendritic cells.

Conclusions:

• Inflammatory activation of MSCs enhances their immune-regulatory functions.
• Activated MSCs can mediate adaptive regulation of proinflammatory pathogenic T-cells.
• This suggests a potential therapeutic role for activated MSCs in autoimmune diseases.