Developmental plasticity allows outside-in immune responses by resident memory T cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Central memory T (T_CM) cells circulate and mediate adaptive immunity.
• Resident memory T (T_RM) cells reside in tissues, providing rapid local protection.
• The plasticity and circulating potential of T_RM cells remain incompletely understood.

Purpose of the Study:

• To investigate the fate and potential of resident memory T cells after reactivation.
• To determine if T_RM cells can transition to other T cell memory subsets.
• To characterize the epigenetic and functional properties of circulating T_RM cells.

Main Methods:

• Isolation and analysis of T_RM cells from the small intestine epithelium.
• Epigenetic profiling of T_RM cells and comparison with other T cell populations.
• In vitro differentiation assays to assess the potential of T_RM cells.
• Tracking of reactivated T_RM cells upon re-entry into the circulation.

Main Results:

• Reactivated T_RM cells rejoined the circulating pool.
• Epigenetic analysis showed T_RM cells resemble conventional memory T cells, not effectors.
• Isolated T_RM cells differentiated into T_CM, effector memory, and T_RM cells.
• Ex-T_RM cells retained tissue-homing predilections and enhanced T_RM redifferentiation capacity.

Conclusions:

• Resident memory T cells are plastic and can transition between tissue-resident and circulating states.
• T_RM cells retain a memory of their tissue of origin and can reform local immunity.
• These findings reveal a dynamic interplay between tissue-resident and circulating memory T cell populations.