FoxP3+RORgammat+ T helper intermediates display suppressive function against autoimmune diabetes

Area of Science:

• Immunology
• Cell Biology
• Autoimmunity

Background:

• Double-positive FoxP3(+)RORgammat(+) T cells were recently identified as potential intermediates for T regulatory (Treg) or T helper 17 (Th17) cell differentiation.
• The precise role and functional capacity of these cells in the context of autoimmune disease remained largely unexplored.

Purpose of the Study:

• To investigate the origin, function, and differentiation potential of FoxP3(+)RORgammat(+) T cell intermediates in the NOD mouse model of type 1 diabetes.
• To determine if these intermediates possess inherent suppressive functions and trafficking capabilities relevant to autoimmune pathology.

Main Methods:

• Analysis of T cell populations in the NOD mouse model.
• Expansion of FoxP3(+)RORgammat(+) cells using tolerogen.
• Assessment of cell surface markers (CD62L, membrane-bound TGF-beta).
• In vitro and in vivo functional assays to evaluate T cell suppression and trafficking.

Main Results:

• FoxP3(+)RORgammat(+) T cell intermediates were found in the NOD mouse T cell repertoire before inflammation onset.
• These intermediates could be expanded with tolerogen without terminal differentiation.
• The cells express CD62L for pancreatic trafficking and membrane-bound TGF-beta for effector T cell suppression.
• FoxP3(+)RORgammat(+) intermediates demonstrated suppressive functions both in vitro and in vivo.
• These cells retain the plasticity to differentiate into FoxP3(+)RORgammat(-) Treg or FoxP3(-)RORgammat(+) Th17 cells upon polarization.

Conclusions:

• FoxP3(+)RORgammat(+) T cells represent a distinct intermediate population with inherent plasticity in differentiation and function.
• These intermediates are poised to traffic to inflammatory sites and suppress pathogenic T cells, potentially broadening therapeutic strategies against autoimmunity.
• The findings suggest a novel mechanism for immune regulation in autoimmune diseases.