Galectin-9 activates and expands human T-helper 1 cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Galectin-9 (Gal-9) exhibits dual roles in T-cell immunity, inducing apoptosis in some T-cell subsets while promoting IFN-γ production in others.
• Previous studies suggest Gal-9 can ameliorate autoimmunity but also has context-dependent effects on T-cell responses.

Purpose of the Study:

• To investigate the immunomodulatory effects of Gal-9 on human resting and activated peripheral blood lymphocytes.
• To delineate the specific mechanisms by which Gal-9 influences T-cell activation, proliferation, and differentiation.

Main Methods:

• Treatment of resting and ex vivo activated human peripheral blood lymphocytes with varying concentrations of Gal-9.
• Flow cytometry analysis to assess T-cell apoptosis, proliferation, phenotype (naïve, memory), and cytokine production (IFN-γ).
• Analysis of CD4/CD8 T-cell balance under different treatment conditions.

Main Results:

• Low concentrations of Gal-9 induced apoptosis in a significant portion of resting T-cells but activated the survivors, leading to expansion and a shift towards central memory and IFN-γ production.
• In the presence of T-cell activation signals, Gal-9 did not promote expansion but shifted the CD4/CD8 balance towards a CD4-dominant response.
• Gal-9 demonstrated the ability to activate resting T-cells independently of typical activation signals.

Conclusions:

• Gal-9 activates resting T-cells and promotes their differentiation into a TH1/C1 phenotype with enhanced immunological memory.
• Gal-9 modulates T-cell immunity by directing CD4-driven responses when T-cell activation signals are present.
• Gal-9 possesses distinct immunomodulatory properties that can enhance reactive immunological memory.