PRODUCTION OF THE RANTES CHEMOKINE IN DELAYED-TYPE HYPERSENSITIVITY REACTIONS - INVOLVEMENT OF MACROPHAGES AND ENDOTHELIAL-CELLS

To understand the selective accumulation of memory T helper lymphocyte s and of macrophages in delayed-type hypersensitivity (DTH) granulomas , we studied the in situ production of RANTES, a chemokine initially c haracterized on the basis of its in vitro chemotactic properties for e ach of these cell populations. RANTES gene expression was studied by i n situ hybridization in 15 human lymph nodes presenting typical DTH le sions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residua l lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated wit h the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distributio n of positive cells in in situ hybridization and immunochemical experi ments indicated that macrophages and endothelial cells, two cell popul ations not previously reported to produce RANTES, contributed to its p roduction in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveol ar macrophages and umbilical vein endothelial cells. In view of the ch emotactic properties of RANTES for a limited range of cell populations , these results suggest that RANTES production in DTH granulomas may p lay a role in the selective accumulation of macrophages and memory T h elper lymphocytes characterizing this type of cell-mediated immune rea ction, and that macrophages and endothelial cells are involved in this production.