Effect of aging on immunological memory in gastrointestinal tract induced by sheep red blood cells in mice.

Tolerance induction by oral administration of sheep red blood cells (SRBC) was investigated in young and aged mice. Two-month old C3H/He mice receiving oral administration of 8 X 10(9) SRBC a day for two weeks became tolerant to a subsequent SRBC challenge in the systemic immune system. In contrast, older C3H/He mice aged about 1 year old receiving the same treatment did not become tolerant but resisted tolerance induction and produced a prominent IgG memory in the systemic immune system. Autoimmune-prone NZB mice showed a similar resistance to tolerance induction even at 3 months of age. To investigate a possible role of the liver in the oral tolerance induction, young (2-month old) C3H/He mice received an injection of 1 X 10(8) SRBC via portal vein. The mice thus treated, were not tolerized at all but immunized. The results suggest that gut-associated local immune system play a key role in the induction of the oral tolerance and that the tolerance inducing function of the local immune system declines with aging. Antigens in the gut including denatured self antigens may immunize the systemic immune system of aged animals.