SUMMARYExtrinsic allergic alveolitis (EAA) (synonym: hypcrsensilivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocylic infiltrates in the pulmonary interstitial tissues. We have previously reported thai the numbers of lymphocytes in bronchoalveoiar iavage (BAL) samples in this disease correlate wilh leveis ofcholesierol and neutral lipid-ladcn 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which areknovtn lobe essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesteroi is capable of enhancing the antigenpresenting function of mononuciear phagocytes by moduiating the expression of HLA-D region products. Ineubation of purified monocytes from heaithy volunteers with cholesterol in serum-free medium induced a significant increase in bolh ihe percentages of monocyles expressing HLA-DQ (P< 002) and in Ihe intensity of expression of the three HLA-D sub-region products, HLA-DQ,-DP and -DR {P<0Q2. <001, <005, respeetiveiy). The choieslerol pre-incubated monocytes also exhibited enhanced antigen-presenting function (/'<005), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augmeni aniigen presentation by modulating the expression of HLA-D region products on anligen-preseniing cells. Apart from EAA. this observation may also have relevance lo inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.