Intracellular Galectin-3 Is Essential for OX40-Mediated Memory CD8⁺ T Cell Development

Area of Science:

• Immunology
• Cellular Biology

Background:

• CD8+ T cells are key for adaptive immunity against pathogens and cancer.
• Costimulation via OX40 enhances T cell responses, partly through IL-2 signaling.
• Galectin-3 (Gal-3) is upregulated in T cells but its role in CD8+ T cell function is unclear.

Purpose of the Study:

• To investigate the role of intracellular Galectin-3 in CD8+ T cell function.
• To determine if Gal-3 regulates the OX40/IL-2 signaling axis in CD8+ T cells.
• To assess Gal-3's impact on CD8+ T cell proliferation, effector function, and survival.

Main Methods:

• Compared wild-type and Galectin-3-deficient murine CD8+ T cells.
• Stimulated T cells via TCR, anti-OX40 mAb, and IL-2.
• Assessed T cell activation, proliferation, survival, and memory formation in vivo.

Main Results:

• Galectin-3 deficiency did not affect early CD8+ T cell activation or proliferation.
• Gal-3-/- CD8+ T cells showed reduced survival and impaired memory cell development.
• Decreased survival in Gal-3-/- T cells was linked to increased apoptosis in a cell-intrinsic manner.

Conclusions:

• Intracellular Galectin-3 is essential for CD8+ T cell survival.
• Gal-3 plays a critical role in OX40-mediated memory formation in CD8+ T cells.
• These findings highlight Gal-3 as a key regulator of adaptive immune responses.