Distinctive CD26 Expression on CD4 T-Cell Subsets

Area of Science:

• Immunology
• Cell Biology

Background:

• CD4 T-cells expressing high CD26 exhibit anti-tumoral properties and are key in chimeric antigen receptor (CAR)-T cell therapies against solid cancers.
• CD26 is also found as soluble sCD26 in biological fluids, with serum levels correlating to T cell subsets, but its relation to enzymatic activity and cell-surface expression is unclear.

Purpose of the Study:

• To investigate the relationship between cell-surface CD26 expression, soluble sCD26, and dipeptidyl peptidase 4 (DPP4) enzymatic activity in CD4 T cells.
• To analyze CD26 expression patterns in different human CD4 T helper cell subsets under various polarization conditions.

Main Methods:

• Ex vivo analysis of cell-surface CD26 on circulating lymphocytes.
• In vitro studies of surface and intracellular CD26 expression in cultured CD4 T cells under different polarization states (Th1, Th2, Th17, Th22, Th0).
• Analysis of sCD26 levels in the secretomes of cultured T cells.

Main Results:

• CD26-negative CD4 T cells are predominantly central memory (TCM) cells, while CD26high expression is found in effector Th1, Th2, Th17, and effector memory (TEM) cells.
• Significant percentages of Th1, Th2, Th17, and Th22 cells were CD26-negative.
• In vitro polarization mirrored ex vivo CD45R0 and CD26 expression patterns.
• sCD26 was present in all secretomes, with levels generally lower in polarized cells compared to the Th0 condition.

Conclusions:

• The study refines understanding of CD26 expression across T helper subsets, potentially improving CAR-T cell therapy design.
• Observed differences in sCD26 levels across T cell subsets may influence the physiological roles of sCD26/DPP4.