Antigen handling in ageing. III. Age-related changes in antigen handling by liver parenchymal and nonparenchymal...

This is a continuation of our earlier studies on antigen handling and the ageing process which have shown the liver to be a major site of antigen retention in the body. This paper reports on the uptake and cellular distribution in relatively pure isolates of the principal cell types of the liver of [35S]sulfanilate-azo-bovine serum albumin (35S-BSA) injected into F-344 rats of ages 4, 12 and 28 months. In all three cell types [hepatocytes (H), Kupffer cells (K) and endothelial cells (E)] antigen retention peaks in the 12-month age class and then exhibits a significant decline in the 28-month age class; K and E cells retain more antigen per cell than do H cells. All three cell types metabolize antigen to nucleopeptides and this transformed antigen is immunologically active; K and E cells metabolize antigen to nucleopeptides more effectively than do H cells. A significant age-related difference is found when nucleopeptides from either H, K or E cells are used to stimulate an antigen-specific lymphoproliferative response in vitro: nucleopeptides from 4-month and 12-month rats stimulate the proliferation of lymphocytes to a significantly higher degree than do nucleopeptides from 28-month old rats. The experiments therefore identify in all three cell populations an age-related defect in antigen uptake and in metabolism of antigen to bioactive nucleopeptides, and they demonstrate that the nonparenchymal cells are more effective in antigen retention and in metabolism of antigen to nucleopeptides than are parenchymal cells. Further, the experiments support the thesis that the liver must be considered to be a principal part of the total immune system, its role much more fundamental than heretofore recognized.