The immunomodulatory effects of TNF during the evolution of the immune response. After TCR ligation, TNF is costimulatory and required for antigen priming. As the immune response proceeds over time, TNF is required to suppress subsequent clonal expansion (TNF+/+; unbroken line). In TNF-deficient animals (TNF-/-; dotted line), immune responses are delayed, but, once established, they fail to resolve, leading to persistent antigen reactivity. TNF, tumour necrosis factor-α.