Although the thymus is primarily noted for the expert of T cells to the periphery, a small influx of cells has also been observed. It is still a matter of debate whether entry into the thymus depends on prier activation. The phenotypes, sources and degree of immigration are largely unknown. We monitored by quantitative immunohistochemistry the entry of cells from the periphery into the rat thymus in three experimental models. We injected i.v. recirculating, small, nonactivated CD4(+) T cell subsets, often referred to as naive (CD45RC(+)) and memory or antigen-experienced (CD45RC(-)) cells, purified from thoracic duct lymph of allotype-marked donors, allotype-marked leukocytes released from spleen or lung transplants, or leukocytes labeled in the periphery for 12 weeks during the S-phase of the cell cycle by oral application of 5-bromo-2-deoxyuridine (BrdUrd). Early after i.v. injection (0.5 h), significantly more antigen-experienced (3D45RC(-)) CD4(+) T cells entered the thymus, and by 24 h four times as many cells from the CD45RC(-) subset as from the CD45RC(+) subset had entered the thymus and localized to the medulla. None of the thymic entrants expressed the interleukin (IL)-2 receptor. Following spleen transplantation similar to 40 % of donor cells entering the thymic medulla were T cells and similar to 55 % were B cells. In contrast, from a lung transplant, similar to 85 % of peripheral immigrants were T cells and similar to 10 % were B cells. After both procedures, a small number of NK cells and monocytes/macrophages were found among the immigrants (< 5 %). Rats were fed BrdUrd continuously for 12 weeks, a procedure which labeled similar to 30 % of peripheral lymphocytes but not cortical thymocytes. BrdUrd-labeled cells were localized almost exclusively to the thymic medulla and represented similar to 10 % of medullary cells. Of the thymic immigrants similar to 50 % were T cells, similar to 30 % were B cells (including similar to 15 % IgD(+) cells), similar to 15 % were NK cells and the remainder (similar to 5%) were monocytes/macrophages. Only a quarter of BrdUrd-labeled cells expressed the IL-2 receptor. The thymus is continuously infiltrated by both activated and nonactivated leukocytes from the periphery, including T cells, B cells, NK cells and monocytes. These immigrants are supplied by lymphoid anti nonlymphoid organs in a characteristic subset composition. Their entry is facilitated by prior antigen experience or activation. Thus, the participation of the thymic medulla in general leukocyte traffic suggests a mechanism by which the T cell repertoire could potentially be modulated by the peripheral tissues.
