Therapeutic monoclonal antibodies against the pro-inflammatory cytokine TNF-α have been successfully used to treat chronic inflammatory diseases. In this issue, Mouritsen and colleagues (p. 666) take this approach one step further by developing a method to immunize against self TNF-α. Mice immunized with modified TNF-α stimulated a booster-dependent T-cell dependent anti-TNF-α response—relieving symptoms of cachexia and arthritis.