TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis

Area of Science:

• Immunology
• Cell Biology
• Molecular Medicine

Background:

• Tumor Necrosis Factor Receptor 2 (TNFR2) is known to be essential for regulatory T cell (Treg) function.
• TNFR2 expression is also induced on effector T cells (Teffs) following T cell receptor (TCR) stimulation.

Purpose of the Study:

• To investigate the role of TNFR2 in pathogenic CD4(+) T cells.
• To determine the impact of TNFR2 deficiency on Teff cell proliferation and function in vivo and in vitro.

Main Methods:

• Adoptive transfer of wild-type (WT) and TNFR2-deficient naive CD4(+) T cells into lymphopenic Rag1(-/-) recipients.
• Assessment of colitis induction, Teff cell expansion, and cytokine production.
• In vitro T cell proliferation assays using anti-CD3 stimulation.
• Analysis of NF-κB signaling pathway components (p100/p52 ratio).

Main Results:

• Transfer of TNFR2-deficient Teff cells resulted in less severe colitis compared to WT Teffs.
• TNFR2-deficient Teff cells exhibited defective proliferative expansion in lymphopenic hosts.
• TNFR2-deficient Teff cells showed reduced expression of pro-inflammatory Th1 cytokines.
• In vitro, TNFR2-deficient naive CD4(+) T cells displayed a decreased proliferative response to TCR stimulation.
• This hypoproliferative phenotype was linked to an increased p100/p52 ratio, suggesting altered NF-κB signaling.

Conclusions:

• TNFR2 plays a significant role in the proliferative expansion of pathogenic effector T cells.
• TNFR2 signaling is critical for the development and exacerbation of T cell-mediated inflammatory diseases.