Tracking antigen-specific T-cells during clinical tolerance induction in humans

Area of Science:

• Immunology
• Allergy Research
• T cell biology

Background:

• Allergen immunotherapy (AIT) aims to induce clinical tolerance.
• Understanding T cell dynamics during AIT is crucial but challenging.
• Existing methods often rely on functional assays, limiting detailed T cell tracking.

Purpose of the Study:

• To develop tools for tracking antigen-specific T cells during wasp venom immunotherapy.
• To investigate T cell responses to Ves v 5, a major wasp venom allergen.
• To elucidate mechanisms of tolerance induction in human AIT.

Main Methods:

• Defined immunodominant regions of Ves v 5.
• Identified HLA-DRB1*1501 restricted epitopes.
• Utilized HLA class II tetrameric complexes and cytokine assays to track T cells during AIT.

Main Results:

• Initial increase in IL-4 producing T cells within 3-5 weeks of AIT.
• Subsequent reduction in circulating effector T cells despite dose escalation.
• Sustained induction of IL-10 and FOXP3+ antigen-specific T cells.
• IL-10+ T cells may share precursors with IL-4+ T cells.

Conclusions:

• Clinical tolerance involves dynamic T cell shifts: loss of IL-4+ and gain of IL-10+/FOXP3+ T cells.
• These T cells can originate from common precursors.
• New T cell tracking methods offer insights into tolerance mechanisms and potential therapeutic targets.