Factors determining T lineage commitment in haematopoietic stem cell.

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T lymphocytes differentiate and mature in the thymus. It has been still controversial whether multi-potent haematopoietic stem cells (HSCs) enter the thymus or progenitors committed to T cell lineage do. It remains also unknown how HSCs are committed to T cell lineage, how a small number of T cells are selected or how mature T cell receptor (TCR) repertoire is formed. Using electron micrographic and immunohistochemical studies, we attempted to isolate HSCs in the thymus of CTS mice (sister strain to NOD, defect in emigration of mature T cells from the thymus to periphery). By using molecular biological technique, we studied thymocyte development and thymic selection in different strains of mice. Novel findings were revealed through these studies.1. We took more than ten thousand electron micrographs and frequently found neutrophils and eosinophils at the stage of development from the myelocyte to the metamyelocyte in the thymic parenchyma. We also isolated erythroids (reticulocytes, er … More ythrocytes) and megakaryocytes. This is the first report to demonstrate that presence of megakaryocytes in thymus, suggesting multi-lineage HSCs enter into the thymus. Cytokine production supporting hematopoiesis in the thymus was confirmed with RT-PCR. Collectively, these results suggest that multi-lineage HSCs immigrate into the thymus.2. TCR repertoire is largely different among different strains of mice in mature thymocytes but not in immature thymocytes at earlier stages. This suggests that pre-selection TCR repertoire is determined by some genetic factors conserved among mouse strains.3. We demonstrated that CDR3 length shortening was occurred in both CD4SP and CD8SP. The extent of CDR3 shortening was remarkable in CD4SP than in CD8SP and varied among different strains of mice, suggesting that the CDR3 shortening was influenced by MHC haplotype. The CDR3 shortening was dependent on V segment. We assumed that structural feature of Vbeta segment encoded in germline impacts on CDR3 length. Less