Gliadin-specific CD4+ effector T cell and pro-inflammatory CD8+ T cell

Gliadin-specific CD4+ effector T cells and pro-inflammatory CD8+ T cells are the central mediators of the pathogenic immune response in Celiac disease. In individuals expressing HLA-DQ2 or HLA-DQ8, CD4+ T cells in the lamina propria recognize deamidated gliadin peptides, leading to the production of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and interleukin-21 (IL-21) (Sollid LM, et al., Nature Reviews Immunology, 2013). This inflammatory environment promotes the activation and expansion of CD8+ intraepithelial lymphocytes (IELs), which express the NKG2D receptor and mediate direct cytotoxic destruction of enterocytes (Jabri B, et al., Nature Reviews Immunology, 2009). Therapeutic interventions targeting these cell populations aim to restore immune tolerance to gluten, thereby preventing intestinal damage without the need for a lifelong gluten-free diet. Current drug candidates, such as TAK-101 (gliadin-encapsulated nanoparticles) and KAN-101 (liver-targeted gliadin peptides), are designed to induce anergy or deletion of these specific T-cell clones (Takeda Pharmaceuticals, 2019; Anokion, 2021). Monitoring these cells often involves the use of HLA-peptide tetramers to track the frequency and phenotype of gluten-specific T cells in patient blood or tissue (Christophersen A, et al., Science Immunology, 2019).

Other names

Gluten-specific T cellsGliadin-reactive T lymphocytesGluten-reactive CD4+ T cellsPro-inflammatory intraepithelial lymphocytes

Induction of antigen-specific immune tolerance, T-cell anergy, or clonal deletion of gluten-reactive lymphocytes.