Clarification of the role of cells constructing the thymic microenvironment in the early T cell development

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We first investigated the role of adhesion molecules in T cell development. Various monoclonal antibodies (mAb) was added into the murine fetal thymus (FT) organ cultures, where T cell development from FT or fetal liver (FL) progenitors was induced by coculturing these cells with a deoxyguanosine-treated FT lobe. We found that anti-Pgp-1, anti-LFA-1 and anti-VLA-4 mAb severely inhibited the early phase of T cell development from FL but not FT.progenitors. These findings strongly suggest that interactions with elements in the thymic microenvironment through Pgp-1, LFA-1, and VLA-4 are indispensable for prethymic progenitors to develop into T cells.We next investigated the role of transcription factors in the early thymic T cell development. We found that the synthesis of TCF-1 and GATA-3 proteins begins simultaneously in a fraction of the most immature population of FT cells, which have the phenotype of CD4^-CD8^-CD44^+CD25^-. It is also found that the T cell development from FL but FT progenitors in the FT organ culture system is severely inhibited by the addition of antisense oligonucleotides for either TCF-1 or GATA-3. These results strongly suggest that TCF-1 and GATA-3 play an essential role in the initiation of the earliest steps of T cell development in the thymus.