TNF receptor distribution in human tissues.

The nature and location of cells responding to tumor necrosis factor-alpha were investigated in situ by immunohistochemistry using monoclonal antibodies directed against the p75 and p55 proteins of the TNF receptor. Receptor expression was found in the thymus and secondary lymphoid tissues. In the thymus, the p75 receptor was confined to medullary lymphoblasts and dendritic cells, which costain with the Tac protein of the interleukin-2 receptor. In lymph nodes and other secondary lymphoid tissues, the p75 receptor was expressed on activated lymphocytes and interdigitating reticulum cells of the T cell areas, whereas the p55 receptor was confined to the germinal center dendritic reticulum cells, which are the main site of TNF-alpha production. TNF receptor proteins were up-regulated in reactive hyperplasia together with increased TNF-alpha expression. Surprisingly, no TNF-R was detectable on nonlymphoid tissues. The species specificity of these TNF-antibodies was high: whereas the antibodies cross-reacted with epitopes in nonhuman primates, no immunoreactivity was detected in lower animal species, e.g., dog, rabbit, and rodents. The data presented suggest that TNF-alpha, which is produced by germinal center DRCs, might regulate an in vivo immune response through autocrine and paracrine pathways, e.g., through the p55 and p75 receptor proteins, which are expressed at different sites on the lymphoid tissue.