Stability of human rapamycin-expanded CD4+CD25+ T regulatory cells

Area of Science:

• Immunology
• Cell Therapy
• T-cell Biology

Background:

• Clinical use of ex vivo-expanded T-regulatory cells is increasing for T-cell-mediated diseases.
• Concerns exist regarding T-regulatory cell purity and in vivo stability, particularly the presence of interleukin-17-producing cells.
• Rapamycin has previously been shown to facilitate T-regulatory cell expansion while inhibiting non-T-regulatory cell proliferation.

Purpose of the Study:

• To investigate the Th17-cell content of T-regulatory cells expanded ex vivo with rapamycin.
• To assess the in vivo stability of rapamycin-expanded T-regulatory cells for cell-based therapy.
• To determine if rapamycin treatment is required to maintain T-regulatory cell phenotype after in vivo transfer.

Main Methods:

• T-regulatory cells were isolated and expanded ex vivo with rapamycin.
• Compared T-regulatory cells cultured with and without rapamycin for regulatory activity, pro-inflammatory cell content, and stability.
• Assessed in vivo stability after transfer into immunodeficient mice.

Main Results:

• Rapamycin-treated T-regulatory cells showed no expansion of contaminating Th17 precursor cells.
• Rapamycin-expanded T-regulatory cells maintained their regulatory phenotype in vitro and after in vivo transfer into mice.
• No additional rapamycin treatment was needed to maintain the phenotype post-transfer.

Conclusions:

• Rapamycin effectively secures ex vivo-expanded human T-regulatory cells.
• These findings support the clinical use of rapamycin-treated T-regulatory cells in cell therapy trials.
• Rapamycin ensures T-regulatory cell purity and stability, addressing safety concerns for therapeutic applications.