Early t-cell interaction with bone marrow stromal cells: implications for t-cell development

Immature T-cells are attracted to bone marrow (BM) stromal cells and an adhesive process takes place. This phenomenon was studied in a coculture system in which selected populations of CD4 CDS double negative (DN) cells adhere to a clonal population of BM stromal cells. In order to understand the mechanism by which T-cell precursors adhere to BM stromal cells, we analyzed the involvement of cytokines and adhesion molecules which may participate in this process and consequently contribute to the preferential cell adherence We found that whereas interleukin-1 did not change the rate of adhesion of thymocytes to the stroma, interferon-y significantly increased cell adhesion. Basic fibroblast growth factor (bFGF) had a dose-dependent biphasic effect on thymocyte adhesion. A greater fraction of DN thymocytes adhered to stroma pretreated with bFGF. Adhesion molecules such as CD49d, CD90, CD44, CD62L and CD2 were found to be necessary participants in this system. The interaction of LFA-1 with ICAM-1, which is crucial in intrathymic T-cell development, seems to play no role in these interactions between immature T-cells and BM stromal cells This suggests that the profile of adhesion molecules involved in the interactions between T-cells and BM stromal cells is different from that in the thymus. Proliferation of T-cells within the stromal layer was revealed by scanning electron microscope examination and verified by cell cycle analysis indicating accumulation of S phase cells. The data of this study imply that BM stromal cells play a crucial role in the early steps of T-cell development.