Isolation of human antigen-specific regulatory T cells with high suppressive function

Area of Science:

• Immunology
• Cell Biology
• Transplantation Immunology

Background:

• Adoptive transfer of regulatory T (Treg) cells is a potential alternative to immunosuppression for preventing allogeneic graft rejection.
• While polyspecific Treg cells manage some immune responses, antigen-specific Treg cells are crucial for treating autoimmunity and graft rejection.
• Current methods lack reliable markers for identifying antigen-specific Treg cells.

Purpose of the Study:

• To identify reliable markers for human antigen-specific Treg cells.
• To evaluate the purity and functional superiority of antigen-specific Treg cells compared to other Treg populations.
• To assess the therapeutic potential of antigen-specific Treg cells in preventing immune responses.

Main Methods:

• Identification of human antigen-specific Treg cells using latency-associated peptide (LAP) and glycoprotein A repetitions predominant (GARP) markers.
• Assessment of Treg-cell purity using epigenetic analysis after CD154(+) cell depletion.
• In vitro and in vivo (humanized mice) functional assays to evaluate Treg cell efficacy in preventing alloreactions.

Main Results:

• Latency-associated peptide (LAP) and glycoprotein A repetitions predominant (GARP) were identified as markers for human antigen-specific Treg cells.
• Depletion of CD154(+) cells from LAP(+) or GARP(+) Treg cells achieved over 90% purity.
• Antigen-specific Treg cells demonstrated superior in vitro function and efficacy in preventing alloreactions in humanized mice compared to other Treg subsets.

Conclusions:

• LAP and GARP serve as reliable markers for isolating antigen-specific Treg cells.
• These antigen-specific Treg cells can be magnetically isolated, facilitating GMP-based protocols.
• Antigen-specific Treg cells possess significant therapeutic potential for managing alloimmune, autoimmune, and allergic responses.