BOTH ACTIVATED AND NONACTIVATED LEUKOCYTES FROM THE PERIPHERY CONTINUOUSLY ENTER THE THYMIC MEDULLA OF ADULT-RATS - PHENOTYPES, SOURCES ANDMAGNITUDE OF TRAFFIC

Although the thymus is primarily noted for the expert of T cells to th e periphery, a small influx of cells has also been observed. It is sti ll a matter of debate whether entry into the thymus depends on prier a ctivation. The phenotypes, sources and degree of immigration are large ly unknown. We monitored by quantitative immunohistochemistry the entr y of cells from the periphery into the rat thymus in three experimenta l models. We injected i.v. recirculating, small, nonactivated CD4(+) T cell subsets, often referred to as naive (CD45RC(+)) and memory or an tigen-experienced (CD45RC(-)) cells, purified from thoracic duct lymph of allotype-marked donors, allotype-marked leukocytes released from s pleen 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), si gnificantly more antigen-experienced (3D45RC(-)) CD4(+) T cells entere d 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 localiz ed to the medulla. None of the thymic entrants expressed the interleuk in (IL)-2 receptor. Following spleen transplantation similar to 40 % o f 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 cel ls. After both procedures, a small number of NK cells and monocytes/ma crophages were found among the immigrants (< 5 %). Rats were fed BrdUr d 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 rep resented 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 r emainder (similar to 5%) were monocytes/macrophages. Only a quarter of BrdUrd-labeled cells expressed the IL-2 receptor. The thymus is conti nuously infiltrated by both activated and nonactivated leukocytes from the periphery, including T cells, B cells, NK cells and monocytes. Th ese immigrants are supplied by lymphoid anti nonlymphoid organs in a c haracteristic subset composition. Their entry is facilitated by prior antigen experience or activation. Thus, the participation of the thymi c medulla in general leukocyte traffic suggests a mechanism by which t he T cell repertoire could potentially be modulated by the peripheral tissues.