Macrophage subpopulations regulate intrathymic T-cell development. I: Ia-positive macrophages augment thymocyte proliferation.

The contribution of H2-Ia-positive thymic macrophages (Ia 1 thymic M phi) to intrathymic lymphopoiesis was investigated. An isolation method yielding cell suspensions highly enriched for Ia+ thymic M phi was performed. Cocultivation of these Ia+ thymic M phi with thymocytes showed that, while not affecting spontaneously proliferating thymocytes, the Ia+ thymic M phi strongly augmented the mitogen-induced proliferation of thymocytes by about 200%. This effect was dependent on the number of Ia+ M phi added as well as on the degree of thymocyte maturity: stronger augmentation occurred at higher concentrations of M phi and immature thymocytes showed highest susceptibility to the Ia+ thymic M phi-mediated effect. Cytochalasin B was employed to prove that cellular interaction is an important prerequisite for the proliferation amplifying effect of Ia+ thymic M phi. Additionally, humoral factors produced by Ia+ thymic M phi after induction with LPS are also involved in the described phenomenon. Furthermore, the use of interleukin preparations in the thymocyte-Ia+ M phi cocultures demonstrated that humoral factors support or probably regulate the interaction of these cells. The implications of these findings in view of the proliferation and differentiation events of thymocytes within the thymus are discussed.