Abstract
Fcγ receptors (FcγRs), composed of a ligand‐binding α‐chain (FcRα) sometimes associated with the homodimeric, cell‐signaling common γ‐chain (FcRγ), comprise an important family of effector molecules linking humoral and cell‐mediated adaptive immunity and regulating innate immunity. In peripheral autoimmune diseases, FcγRs contribute to inflammation and tissue damage through inappropriate activation of macrophages and neutrophils, release of cytokines and oxidants, and destruction of autoantibody‐opsonized cells. In the central nervous system (CNS), the role of FcγRs in autoimmune disease such as multiple sclerosis (MS) remains largely unexplored despite extensive documentation of CNS‐specific antibodies in cerebrospinal fluid and plaques. Several studies have now examined the role of FcγRs in experimental autoimmune encephalomyelitis (EAE), the animal model for MS, using mice genetically deficient in one or more FcγRs or in FcRγ. These studies indicate that none of the FcγR α‐chains are critical for EAE development and progression. In contrast, it is unequivocal that FcRγ contributes to EAE, and surprisingly it seems that this effect is independent of FcγRs. Recent studies now indicate that FcRγ expression in γδ T cells, most likely as a component of the TCR/CD3 signaling complex, is a critical requirement for EAE development. These studies support previous evidence implicating a pathogenic role for γδ T cells in EAE. © 2004 Wiley‐Liss, Inc.