Isolated CD39 expression on CD4+ T cells denotes both regulatory and memory populations

Area of Science:

• Immunology
• Cell Biology

Background:

• Foxp3(+) regulatory T cells (Tregs) utilize CD39 and CD73 ectoenzymes to metabolize ATP into adenosine, a key immunosuppressive molecule.
• The CD4(+)CD39(+) T-cell population in mice comprises both Foxp3(+) Tregs and Foxp3(-) cells with distinct phenotypes and functions.

Purpose of the Study:

• To investigate the role and characteristics of CD39-expressing T cells beyond canonical Tregs.
• To understand the functional implications of CD39 expression on different T-cell subsets, particularly memory T cells.

Main Methods:

• Utilized Foxp3GFP knockin mice for T-cell subset identification.
• Phenotypic analysis (CD44, CD62L, CD25, CD73) and functional assays including cytokine expression, TGF-beta induction inhibition, and skin allograft rejection.

Main Results:

• Identified two major CD4(+)CD39(+) T-cell populations: CD73(bright) Foxp3(+) Tregs and CD73(dim/-) Foxp3(-) cells with a memory phenotype (CD44(+)CD62L(-)CD25(-)).
• CD39 expression protects both Tregs and memory T cells from ATP-induced apoptosis.
• Foxp3(-)CD39(+) memory T cells exhibit heightened expression and secretion of Th1, Th2, and Th17 cytokines, inhibit TGF-beta-induced Foxp3 expression in naive T cells, and accelerate skin allograft rejection.

Conclusions:

• CD39 is not exclusively expressed on Tregs but also on pre-existing memory T cells of Th1, Th2, and Th17 lineages.
• These CD39(+) memory T cells possess heightened alloreactivity and can modulate Treg function, suggesting a broader role for CD39 in immune regulation and T-cell responses.