Regulatory T Cells Inhibit T Cell Activity by Downregulating CD137 Ligand via CD137 Trogocytosis

Area of Science:

• Immunology
• Cell Biology

Background:

• CD137 (4-1BB) is a costimulatory molecule on activated T cells.
• CD137 ligand (CD137L) on antigen-presenting cells (APCs) enhances immune responses.
• CD137 expression on regulatory T cells (Treg) and its function are controversial.

Purpose of the Study:

• Investigate the function of CD137 expressed on Treg.
• Elucidate the mechanism by which Treg modulate immune responses via CD137 and CD137L.

Main Methods:

• Utilized human and murine cell co-cultures.
• Analyzed trogocytosis of CD137 and CD137L between Treg and APCs.
• Examined the role of CD137 signaling and truncated CD137 forms.

Main Results:

• Treg expressing CD137 bind to CD137L on APCs.
• Trogocytosis results in the transfer of CD137 or CD137L, forming a complex.
• This process internalizes CD137-CD137L complexes, downregulating CD137L on APCs.
• CD137 signaling is not required for CD137L downregulation.

Conclusions:

• Treg utilize trogocytosis of CD137 and CD137L as a novel mechanism to control immune responses.
• By downregulating immunostimulatory CD137L on APCs, Treg exert inhibitory functions.
• This CD137-CD137L trogocytosis mechanism is conserved across species.