Skeletal muscle can be both the site and target of immune reactions. Here, Reinhard Hohlfeld and Andrew Engel consider the role of muscle as an immunological microenvironment and discuss the immunological properties of human muscle cells. Furthermore, they provide ab, ief overview of autoimmune diseases of muscle and of other conditions in which intramuscular immune reactions play a role. Finally, they discuss the immunological problems of novel gene therapies that rely on muscle cells as vehicles for gene transfer.

Muscle fibers are large syncytial cells specialized to generate mechanical force. Large mature fibers contain hundreds of nuclei that are normally positioned under the plasma membrane (Fig. 1). The cytoplasm contains highly organized bundles (fibrils) of protein filaments that interact to generate the force of muscle contraction. Each muscle fiber is innervated by a branch of a motor neuron, which contacts the fiber at the neuromuscular junction. This junction is a chemical synapse at which acetylcholine (ACh) acts as the transmitter 1. ACh is released from the nerve terminal, diffuses across the synaptic cleft and binds to acetylcholine receptors (AChR) that are located in the specialized area of muscle membrane opposite the nerve terminal. Each AChR molecule contains a central ion channel that opens after ACh binds to AChR, allowing influx of small cations. This leads to depolarization of the subsynaptic muscle-fiber membrane and generates an action potential that spreads along the muscle fiber, initiating the chain of events that e,-entua!! y leads to contraction.