6533b831fe1ef96bd1298383

RESEARCH PRODUCT

PROMOTION OF INTRATHYMIC T-CELL DEVELOPMENT BY MHC-Ia-POSITIVE THYMIC MACROPHAGES (Ia + Mø)

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description

The generation of the peripheral T-cell pool is attributed to maturation and differentiation events occurring within the thymus. Three thymic compartments, thymic epithelial cells, thymic hormons and thymic Mo are considered to contribute to the intrathymic T-cell development. While, as we have shown earlier, murine as well as human MHC-Ia-negative-Mo (Ia−Mo) regulate thymocyte (TH) differentiation via suppressive effects (Thymus,6:295,1984) and MHC-Ia+-Mo are involved in intrathymic tolerance induction (Pediatr Res,15:800, 1984), now the contribution of Ia+Mo to intrathymic lymphopoiesis was investigated. An isolation method yielding cell suspensions highly enriched for Ia+ thymic Mo was performed (BSA-gradient,antibody treatment,irradiation). Cocultivation of these Ia+Mo with TH showed that Ia+Mo strongly augmented the mitogen-induced proliferation of TH by about 200%. The effect was dependent on the number of Ia+Mo added and on the degree of TH maturity: stronger augmentation occurred at higher Mo concentrations immature TH showed highest susceptibility to the Ia+Mo mediated effect. Cell-cell-contact was an important prerequisite for the proliferation amplifying effect as demonstrated by use of Cytochalasin B. In addition, humoral factors produced by Ia+Mo also improved the proliferative capacity of TH, similar to results obtained using interleukin II. The results described support the view that thymic Mo populations act as a main regulatory principle in T-cell development. Ia+Mo augment intrathymic lymphopoiesis and participate in tolerance induction,while Ia−Mo control the number of TH finally leaving the thymus gland.