Autoreactive citrullinated peptide-specific CD4+ T lymphocyte (Cit-specific CD4+ T cell) (Cit-specific CD4+ T cell)

Autoreactive citrullinated peptide-specific CD4+ T lymphocytes are a specialized subset of helper T cells that recognize post-translationally modified proteins where arginine residues have been converted to citrulline (Malmström et al., 2017, Nature Reviews Rheumatology). This recognition is highly associated with the HLA-DRB1 "shared epitope" alleles, which are the strongest genetic risk factors for rheumatoid arthritis (RA) (Scally et al., 2013, Nature Genetics). These T cells drive the autoimmune process by promoting the production of anti-citrullinated protein antibodies (ACPAs) by B cells and by infiltrating the synovium to release pro-inflammatory cytokines like IL-17 and TNF-alpha (Hill et al., 2003, J Exp Med). Targeting these cells is a major focus of precision medicine in RA, with therapies like Rheumavax (DEN-181) aiming to induce immune tolerance or selectively inhibit their activation to halt disease progression while preserving overall immune function (Thomas et al., 2015, Science Translational Medicine). Other approaches include costimulation blockade with Abatacept, which interferes with the activation of these autoreactive clones by blocking the CD28-CD80/86 pathway. The identification of these cells using MHC class II tetramers has enabled better monitoring of disease activity and response to therapy. Overall, these cells represent a critical link between genetic susceptibility and the clinical manifestation of ACPA-positive rheumatoid arthritis.

Other names

Citrullinated peptide-specific CD4+ T cellsACPA-specific T cellsCCP-reactive CD4+ T cellsCitrulline-specific T cellsAnti-citrullinated protein antibody-associated T cells

Modulation of T cell activation via costimulation blockade or induction of antigen-specific peripheral tolerance through peptide-loaded dendritic cells or nanoparticles.