Failure of lymphokine-producing lymphocytes from aged humans to undergo activation by recall antigens

In order to understand better the causes of diminished delayed hypersensitivity in the elderly, we studied lymphocyte function in 10 healthy subjects over 80 years of age. Markedly decreased antigen-stimulated lymphokine production (3 of 30 assays positive versus 24 of 31 in young control subjects) was the most significant finding in the elderly subjects and appeared to be the best explanation for their reduced cutaneous responses to recall antigens. Although mitogen-stimulated lymphocyte transformation in the elderly group was more sensitive to suppression by prostaglandin E2 than that of the young group, direct prostaglandin action did not appear to explain the diminished antigen-stimulated lymphokine responses. The nonspecific mitogen concanavalin A elicited normal lymphokine responses in 9 of 10 elderly subjects, indicating that lymphocytes from the elderly have a normal capacity for lymphokine production when activated by a sufficient stimulus. Therefore, diminished delayed hypersensitivity in aged humans may be related to deficient lymphokine production, which in turn appears to involve a decreased capacity of the lymphocytes producing these mediators to undergo activation by recall antigens.