Cellular interactions in the thymic microenvironment
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The haemopoietic multipotential stem cell differentiates in distinct maturational pathways to generate different populations of blood cells. Differentiation and proliferation within the thymus is a prerequisite of precursors committed to the T-lymphocyte lineage. These differentiative events involve an interaction with the non-lymphoid cells of the thymus. Monolayers derived from the non-lymphoid stromal elements of the murine thymus were established and maintained in vitro. The cells in culture were characterised on the basis of their morphological and functional features. They were found to be morphologically heterogenous at the light microscopical and ultrastructural level, and largely phagocytic. The possible maturation inducing properties of the cultured thymus cells were investigated. The PHA responsiveness of thymocytes, a feature of more mature lymphocytes was found to be marginally enhanced upon co-culture with these cells or after incubation in their conditioned medium. Similar effects were obtained with monolayers derived from peritoneal, exudate cells, but to a lesser extent. A method of depleting the endogenous lymphoid cells in explants of embryonic thymic tissue in culture was established, enabling the enrichment of the epithelial component. These epithelial thymuses were reconstituted with early undifferentiated haemopoietic cells and more mature lymphoid precursors in vitro. The latter were found to readily repopulate the explants, whereas the less differentiated cells did not. The lymphocytic cells of the bone marrow were isolated by differential centrifugation. The enriched cells were used as targets to investigate the possible differentiation inducing properties of the thymic monolayer cells, as well as their own capacity to repopulate the thymus in vitro. They were found to be refractory to any such maturational induction, and their thymus-seeding ability was not conclusively resolved. The significance of these findings are discussed with regard to the maturational potential of different haemopoietic cells in the lymphomyeloid tissues. The cell proliferation kinetics of the thymus during late gestation was investigated. The cell production rate was found to be greatly diminished in pregnancy, during which the spleen was found to sustain an increased extra-medullary erythropoietic activity. The responsiveness to PHA during pregnancy was investigated. The possible causes and consequences of haemopoietic imbalance are discussed, especially with regard to the possibly impaired immune competence of the pregnant animal.
Thesis, PhD Doctor of Philosophy
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