Involution of the thymus revisited: immunological trade-offs as an adaptation to aging

An attempt was made, in previous theories, to find a unifying explanation for two phenomena of thymic involution: stress-induced reversible involution and age-related irreversible involution. It was postulated that in both cases involution is beneficial to the organism, as it serves to reduce the dangers of autoimmune reactions. The modified theory proposed here: (a) relates to the suggestions of I.R. Cohen and D.B. Young (Immunol. Today, 12 (1991) 105-109) and to those of S. Avrameas Immunol. Today, 12 (1991) 154-158) as to the usefulness of autoantibodies to the organism; (b) emphasizes the fact that self components undergo continuous changes throughout the life cycle of the organism, which in turn necessitates continuous adaptations to prevent autoimmune damage; (c) stresses the relevance of these adaptations to the process of natural selection; (d) brings experimental evidence to the effect that thymic involution will reduce the danger of autoimmune damage; and (e) suggests that the adaptations required to prevent autoimmune reactions with aging entail immunological compromises or trade-offs. These measures may by themselves cause autoimmune diseases, result in reduced resistance to neoplasia and to infectious diseases, particularly viral ones, and in accelerated aging.