4-1BBL costimulation retrieves CD28 expression in activated T cells.

Area of Science:

• Immunology
• Cellular Biology
• Molecular Biology

Background:

• CD80/86 binding to CD28 is a primary T cell costimulatory signal.
• CD28 expression rapidly declines post-T cell activation.
• The interplay between CD137 (4-1BB) and CD28 signaling remains incompletely understood.

Purpose of the Study:

• To investigate the cross-interaction between CD137 (4-1BB) and CD28 signaling pathways.
• To determine the effect of CD137 signaling on CD28 expression and T cell proliferation.
• To explore the potential of CD137 for ex-vivo T cell activation and expansion.

Main Methods:

• T cells were stimulated with anti-CD3 and engineered A549 lung carcinoma cells expressing CD80/CD86 and/or 4-1BBL.
• Flow cytometry was used to analyze CD28 expression on CD4(+) and CD8(+) T cells.
• T cell proliferation was monitored under different costimulatory conditions.

Main Results:

• CD80/86 costimulation led to rapid CD28 downregulation and reduced proliferation.
• Costimulation with 4-1BBL alone maintained CD28 expression.
• 4-1BBL costimulation restored CD28 expression and proliferation in T cells that had downregulated CD28 due to CD80/86 engagement.

Conclusions:

• CD137 signaling positively influences CD28 expression, counteracting CD28 downregulation.
• This interaction suggests a reciprocal relationship between CD28 and CD137 signaling.
• Signals through CD137 are crucial for sustained ex-vivo T cell activation and expansion.