antigen handling in ageing iii agerelated changes in antigen handling by liver parenchymal and nonparenchymal cells 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 35ssulfanilateazobovine serum albumin 35sbsa injected into f344 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 12month age class and then exhibits a significant decline in the 28month 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 agerelated difference is found when nucleopeptides from either h k or e cells are used to stimulate an antigenspecific lymphoproliferative response in vitro nucleopeptides from 4month and 12month rats stimulate the proliferation of lymphocytes to a significantly higher degree than do nucleopeptides from 28month old rats the experiments therefore identify in all three cell populations an agerelated 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