Thy-1 stimulation of mouse T cells induces a delayed T cell receptor-like signal that results in Ca2+-independent cytotoxicity

Abstract

Antibody-mediated crosslinking of Thy-1 [also known as cluster of differentiation (CD)90], results in a T cell receptor (TcR)-like signal; however, the impact of Thy-1 stimulation in comparison to TcR stimulation on T cell activation and effector function has yet to be fully elucidated. In the present study, the outcome of Thy-1- and TcR-induced stimulation of T cells was investigated in mice, using fragment crystaliz-able (Fc) receptor-bound antibodies and costimulatory signals provided by syngeneic lipopolysaccharide-matured bone marrow-derived dendritic cells. Compared with TcR signaling, Thy-1 signaling initiated a less robust proliferative response in T cells, as determined by tritiated-thymidine incorporation. In addition, enzyme-linked immunosorbent assays revealed that interleukin-2 production was reduced, and the expression of CD25 and cyclin D3 was weaker in Thy-1-stimulated cells, as determined by western blotting; however, the expression of cyclin-dependent kinase 6 was similar to that in TcR-induced T cells. Furthermore, western blotting demonstrated that the phosphorylation of ς-chain-associated protein kinase 70 and extracellular signal-regulated kinase 1/2 was delayed following Thy-1 stimulation. DNA fragmentation assays revealed that cytotoxic effector function was also slower to develop in Thy-1-stimulated T cells, required more time to be effective and was largely Ca2+-independent; these findings suggested that Fas ligand rather than granule-associated perforin was involved in T cell effector function. In conclusion, the present results suggested that Thy-1 signaling may contribute to the regulation of T cell homeostasis and the development of non-specific T cell-mediated cytotoxicity. However, further studies are required to elucidate the exact physiological roles of TcR-like signals that result from Thy-1 crosslinking and to investigate the molecular mechanisms that are involved.