CD4(+) CD25(low) GITR(+) cells: a novel human CD4(+) T-cell population with regulatory activity

Area of Science:

• Immunology
• Cell Biology

Background:

• Regulatory T cells (Tregs) are crucial for maintaining peripheral tolerance.
• Tregs are typically identified by markers like FOXP3 and CD25 and produce suppressive cytokines (IL-10, TGF-β).
• Glucocorticoid-induced TNF receptor family-related (GITR) protein's role in human Treg activity is not well-defined.

Purpose of the Study:

• To investigate GITR expression in human CD4(+) T lymphocytes.
• To determine the function of GITR-expressing human T cells in Treg activity.

Main Methods:

• Flow cytometry to identify CD4(+) T cell subsets expressing GITR and CD25.
• Analysis of FOXP3, cytokine, CTLA-4, and CD127 expression.
• Functional assays to assess suppressive activity and the effect of anti-GITR antibody.

Main Results:

• A distinct subset of human CD4(+) T cells expressing GITR and low CD25 (CD4(+) CD25(low) GITR(+)) was identified.
• These cells express FOXP3, IL-10, and TGF-β, exhibit anergy, and possess suppressive activity dependent on TGF-β.
• Unlike natural Tregs, CD4(+) CD25(low) GITR(+) cells have low CTLA-4 and high CD127 expression.
• Anti-GITR antibody inhibited the suppressive activity of these cells.

Conclusions:

• Human CD4(+) CD25(low) GITR(+) cells represent a unique subpopulation of regulatory T cells.
• GITR plays a significant role in regulating the suppressive function of this distinct Treg subset.