Requirement of cell interactions through adhesion molecules in the early phase of T cell development

We investigated the role of adhesion molecules in T cell development. A large proportion of murine fetal thymus (FT) cells obtained at Day 13 of gestation, which are c-kit+, express the adhesion molecules Pgp-1, VLA-4, LFA-1, and ICAM-1 on their surface at high levels. The expression profiles of these adhesion molecules resemble quite well those on c-kit+ cells in fetal liver (FL). The level of expression of these molecules on FT cells declines with the embryonal age and becomes mostly negative by birth except for LFA-1. In the case of LFA-1, a reincrease of expression levels is seen in newborn mice. The role of these adhesion molecules in T cell development was investigated by adding monoclonal antibodies (mAb) into the FT organ cultures, where T cell development from FT or 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 progenitors. On the other hand, the suppressive effect of these mAb on the T cell development from FT progenitors was only slight, if any. 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.