THY-1 FUNCTIONS AS A RECOGNITION SIGNALING MOLECULE DURING MOUSE T-LYMPHOCYTE DEVELOPMENT/

Thy-1 is a prototype of mammalian glycosyl phosphatidylinositol (GPI)- anchored molecules and belongs to the Ig superfamily. This cell surfac e glycoprotein is expressed on mouse T lymphocytes, neurons and hemato poietic stem cells. Despite detailed structural studies, little is kno wn about the physiological role(s) of Thy-1. We discuss here our resul ts on the role of Thy-1 in immature T lymphocytes during intrathymic m aturation. It was observed that Thy-1-mediated adhesion of mouse thymo cytes to thymic stromal cells occurs through interaction with an unkno wn ligand. The interaction occurs by a Ca2+-independent mechanism and does not require TCR/CD3 surface expression. To evaluate the signal tr ansduction upon Thy-1 ligation in immature thymocytes, we cultured mou se thymocytes with monoclonal antibodies specific for Thy-1, immobiliz ed onto the tissue culture plates. Monoclonal antibodies directed at d eterminants located in a defined epitope domain, but not others, trigg ered marked physiological cell death (apoptosis) of immature thymocyte s, as evidenced by morphological and biochemical data. This apoptosis is independent of the cell surface expression of TCR/CD3. It is a deve lopmentally regulated process since the period in which thymocytes are sensitive to Thy-1-dependent apoptosis corresponds to the development al ''window'' during which massive death of immature thymocytes takes place within the thymus. Therefore, we propose that Thy-1 could functi on as a cell survival/death regulator in mouse T lymphocyte developmen t.