Circulating macrophages as well as developing thymocytes are enclosed within thymic nurse cells

Both thymic nurse cells (TNCs) and macrophages have been reported to functi on as antigen-presenting cells during the process of MHC restriction. Negat ive selection, which results in the apoptosis of potentially autoreactive t hymocytes, is believed to be associated with both macrophages and TNCs in t he cortex. Both cell types have also been reported to ingest thymocytes und ergoing positive and negative selection. However, macrophages ingest apopto tic thymocytes, while TNCs have been shown to internalize viable cells. A s ubset of the TNC-engulfed population is allowed to mature and is released, while the remaining fraction becomes apoptotic and is absorbed within the T NC cytoplasm through lysosomal activity. A recent report described a subset of rat TNCs that contain macrophages as well as thymocytes within their cy toplasm. We examined freshly isolated TNCs from C57BL/6 mice and found that , of the TNC population recovered, 1.7% contained macrophages within its cy toplasm. There also were macrophages tightly bound but not internalized int o the multicellular structure at a rate of 2.9%. The total association of m acrophages with TNCs was approximately 4.6%. This unique association of mac rophages with TNCs was also observed in vitro when freshly isolated thymocy tes (containing macrophages) were added to cultures of cells from the TNC c ell line tsTNC-1. The macrophage-TNC interaction was found to be dynamic, w ith macrophages moving rapidly into and out of TNCs containing cytoplasmic thymocytes. Macrophages within TNCs showed a close association with cytopla smic thymocytes. We then labeled peritoneal macrophages with CFDA SE, a cel l tracking dye, and returned them to the mouse peritoneum. Within 1 h, labe led macrophages were detectable in the thymus. This is the first investigat ion to show a direct interaction between peripheral macrophages and TNCs. T hese results suggest that TNCs and macrophages work together as antigen-pre senting cells. (C) 2001 Academic Press.