T Cell-Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The CD27-CD70 pathway typically provides T cell costimulation.
• CD70 expression on antigen-presenting cells (APCs) and CD27 on T cells are established.
• The function of CD70 expressed directly on T cells remains largely unknown.

Purpose of the Study:

• To investigate the role of T cell-derived CD70 in regulating T cell responses.
• To elucidate the mechanisms by which T cell CD70 influences immune pathology.

Main Methods:

• Adoptive-transfer models of autoimmune inflammatory bowel disease (IBD).
• Allogeneic graft-versus-host disease (GVHD) models.
• Analysis of T cell expansion, cytokine production, apoptosis, and immune checkpoint molecule expression.

Main Results:

• T cells lacking CD70 (CD70-/-) exacerbated IBD and GVHD, producing higher inflammatory cytokines.
• IFN-γ induces CD70 expression on T cells.
• CD70 limits T cell expansion through caspase-dependent apoptosis and upregulation of inhibitory immune checkpoints, independent of regulatory T cells.
• T cell-intrinsic CD70 signaling contributes to this inhibitory checkpoint function.

Conclusions:

• T cell-derived CD70 functions as a novel immune checkpoint, inhibiting inflammatory T cell responses.
• This study identifies a critical negative feedback role for T cell CD70 in downregulating T cell-mediated inflammation.