The life (and death) of CD4⁺CD28^null T cells in inflammatory diseases

Inflammation contributes to the development and perpetuation of several disorders and T lymphocytes orchestrate the inflammatory immune response. Although the role of T cells in inflammation is widely recognized, specific therapies that tackle inflammatory networks in disease are yet to be developed. CD4⁺CD28^null T cells are a unique subset of helper T lymphocytes that recently shot back into the limelight as potential catalysts of inflammation in several inflammatory disorders such as autoimmunity, atherosclerosis and chronic viral infections. In contrast to conventional helper T cells, CD4⁺CD28^null T cells have an inbuilt ability to release inflammatory cytokines and cytotoxic molecules that can damage tissues and amplify inflammatory pathways. It comes as no surprise that patients who have high numbers of these cells have more severe disease and poor prognosis. In this review, I provide an overview on the latest advances in the biology of CD4⁺CD28^null T cells. Understanding the complex functions and dynamics of CD4⁺CD28^null T cells may open new avenues for therapeutic intervention to prevent progression of inflammatory diseases.