How do immune cells communicate and coordinate their attacks? This review explores the role of CD40-CD154 interactions in cell-mediated immunity, highlighting their importance beyond B-T cell communication. CD40, expressed on diverse cell types including dendritic cells and macrophages, interacts with CD154, influencing a wide range of immune responses. Studies using CD40- and CD154-knockout mice, along with antibodies targeting these molecules, have helped elucidate the role of this system in immune regulation. This paper shows that CD40-CD154 interactions influence T cell priming and effector functions, upregulate costimulatory molecules, and activate macrophages, NK cells, and endothelia. The discussion spans the involvement of this system in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. The review focuses on the evolving understanding of CD40-CD154 in inflammation and cell-mediated immunity, pointing to how it influences T cell priming and T cell-mediated effector functions. The upregulating costimulatory molecules and activating macrophages, NK cells, and endothelia have also been noted. This research underscores the CD40-CD154 system is central to inflammation and cell-mediated immunity. Understanding these interactions could pave the way for new therapeutic interventions in autoimmune diseases and other immune-related disorders.
Published in the Annual Review of Immunology, this comprehensive review aligns with the journal's focus on cutting-edge research in immunology. By focusing on CD40-CD154 interactions and their multifaceted roles in immune responses, it addresses a central and rapidly evolving area of immunological research.