Macrophage subpopulations regulate intrathymic T-cell development. II: Ia-negative macrophages decrease thymocyte viability and proliferation by formation of thymocyte-macrophage-rosettes.

The influence of H2-Ia-negative macrophages (Ia-M phi) on thymocyte viability and proliferation was investigated. Peritoneal as well as Ia-M phi of thymic origin were used in this study and yielded similar results. Cocultivation of thymocyte with 4.5% Ia- M phi diminished thymocyte viability by about 70% and mitogen-induced proliferation by about 90% in comparison to control cultures without addition of M phi. These suppressive effects were related to rosette formation between thymocytes and Ia- M phi: more than 80% of Ia- M phi formed rosettes with immature thymocytes. Mature thymocytes (i.e. PNA-negative, steroid-resistant cells) rosetted in only 5% and were consequently not affected by M phi-mediated suppression. Since Cytochalasin B, known to inhibit rosette formation, abolished the suppressive effects of M phi, and supernatants of M phi cultures exhibited no inhibition of thymocytes, close cell contact (rosette) is apparently necessary for the inhibitory phenomenon. Suppression, however, seems to depend further on the functional state of the M phi: ingestion of carbon particles significantly diminished the inhibitory effect on thymocytes despite further presence of rosettes. The results suggest that Ia- M phi have a regulatory function within thymus physiology. While Ia+ M phi promote thymocyte proliferation as described elsewhere, the Ia- M phi may control the number and kind of thymocytes released by the thymus gland.