γδ T Cells Activated in Different Inflammatory Environments Are Functionally Distinct.

Area of Science:

• Immunology
• T cell biology

Background:

• Gamma delta T cells play a critical role in regulating autoimmune diseases like experimental autoimmune uveitis (EAU).
• Their function, whether disease-promoting or protective, depends on their activation state.
• Understanding how different activation pathways influence gamma delta T cell function is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate how distinct activation methods and inflammatory conditions affect the function of gamma delta T cells.
• To determine the impact of surface CD73 expression levels on gamma delta T cell activity.
• To explore the polarization of gamma delta T cells into specific functional subsets, similar to alpha beta T cells.

Main Methods:

• Activation of gamma delta T cells using anti-CD3 antibodies and inflammatory cytokines.
• Analysis of surface CD73 expression following activation by cytokines and dendritic cells.
• Assessment of gamma delta T cell polarization into Th17-like (gdT17) and Th1-like (gdT1) subsets under specific polarizing conditions.

Main Results:

• Different activation pathways lead to distinct gamma delta T cell functions, with anti-CD3 activating both IFN-γ+ and IL-17+ cells, while cytokines favor IL-17+ cells.
• Gamma delta T cells maintain high CD73 expression after cytokine exposure but downregulate it upon interaction with dendritic cells.
• CD73low gamma delta T cells exhibit reduced inhibitory capacity compared to CD73high cells, despite both having disease-enhancing effects.
• Gamma delta T cells can be polarized into gdT17 (IL-17 producing) and gdT1 (IFN-γ producing) subsets, with gdT17 cells mediating pro-Th17 activity.

Conclusions:

• The functional activity of gamma delta T cells is significantly modulated by the activation pathway and inflammatory milieu.
• Surface CD73 expression serves as a marker differentiating gamma delta T cell subsets with varying immunoregulatory potential.
• Gamma delta T cells exhibit functional polarization, analogous to other T cell types, influencing their role in autoimmune responses.