Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to...

Area of Science:

• Immunology
• Pharmacology
• Molecular Biology

Background:

• CD4+ T cells are crucial for adaptive immunity.
• Co-stimulatory molecules like ICOS and OX40 regulate T cell activation and proliferation.
• The precise mechanisms of azithromycin's (AZM) immunomodulatory effects, particularly on T cells, remain unclear.

Purpose of the Study:

• To investigate the in vitro effects of AZM on CD4+ T cell proliferation.
• To examine AZM's impact on the co-stimulatory molecules ICOS and OX40.
• To elucidate the molecular pathways involved in AZM-mediated T cell suppression.

Main Methods:

• Utilized multi-color flow cytometry on TCR-activated peripheral blood mononuclear cells from healthy donors.
• Assessed surface expression and frequencies of ICOS and OX40 receptors.
• Measured cell proliferation and mTOR activity via S6 ribosomal protein phosphorylation.

Main Results:

• AZM treatment significantly reduced the frequencies and surface expression of ICOS and OX40 on CD4+ T cells.
• AZM-treated ICOS+ and OX40+ T cells exhibited profoundly reduced proliferation compared to their untreated counterparts.
• Suppressed mTOR activity, indicated by decreased S6 ribosomal protein phosphorylation, was observed in AZM-treated T cells.

Conclusions:

• AZM inhibits CD4+ T cell proliferation by targeting co-stimulatory pathways involving ICOS and OX40.
• AZM-induced suppression of T cell proliferation is associated with reduced mTOR signaling.
• This study provides novel insights into the mechanism of AZM's immunomodulatory actions on T lymphocytes.