Pathogenic autoreactive CD4+ T cell

Pathogenic autoreactive CD4+ T cells are a specialized subset of helper T lymphocytes that have escaped central or peripheral tolerance and mistakenly recognize self-peptides presented by Major Histocompatibility Complex class II (MHC-II) molecules [1]. These cells play a central role in the pathogenesis of various autoimmune diseases, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, by orchestrating an inflammatory response against host tissues [3]. Upon activation, they differentiate into effector phenotypes such as Th1 or Th17 cells, secreting potent pro-inflammatory cytokines like interferon-gamma (IFN-γ) and interleukin-17 (IL-17) that recruit and activate other immune cells [1, 3]. They also provide essential help to B cells, promoting the production of high-affinity autoantibodies. Therapeutic interventions aim to selectively deplete these cells, inhibit their activation through costimulatory blockade, or prevent their migration into target organs [4]. For example, anti-CD3 antibodies like teplizumab are used to modulate these cells in type 1 diabetes, while costimulation blockers like abatacept prevent their full activation [2, 4]. Emerging precision therapies, such as antigen-specific tolerization and engineered T-cell approaches, seek to neutralize these pathogenic cells without compromising the broader protective immune system.

Other names

Self-reactive CD4+ T cellAutoreactive T helper cellPathogenic T effector cellTh1/Th17 autoreactive cell

T-cell depletion, inhibition of costimulation, blocking of leukocyte trafficking, and induction of immune tolerance.