This is in part due to the fact that CD58 lacks

a murine orthologue and demonstrates the current emphasis on mouse model systems to study the costimulatory 3-MA datasheet pathways. There are an ever growing number of ligands that have been implicated to play a role in T cell costimulatory processes and contradictory results have been reported for several of these molecules (Leitner et al., 2010). We believe that T cell stimulator cells are especially suited to assess the function of accessory molecules during T cell activation since they allow analyzing human T cell responses under conditions that only differ regarding the presence of the molecules of interest. We have recently used stimulator cells expressing PD-L2 and B7-H3, two members of the extended B7 family, to address their function during the activation of human T cells (Pfistershammer et al., 2006 and Leitner et al., 2009). In these studies we could show that these molecules consistently inhibited T cell responses and our experiments did give any evidence for positive costimulatory functions for human PD-L2 and B7-H3. The CD2 superfamily member CD150 and the TNF-SF member TL1A have both been described to costimulate T cell activation. CD150 is a self-ligating receptor, whereas TL1A binds to DR3 a member of the TNFR-SF. However, AC220 few studies

on these molecules have directly analyzed the consequences of the interaction of CD150 or TL1A with human T cells. In the present study we have generated T cell stimulator cell

lines expressing CD150 and TL1A and used them to stimulate purified human T cells. Our results demonstrate that the presence of TL1A during T cell activation significantly costimulates their proliferation and production of cytokines, whereas T cells stimulated in the presence of stimulator cells expressing CD150 did not show enhanced proliferation and cytokine production. Previous studies that have described a positive costimulatory function for CD150 have used antibodies to Liothyronine Sodium crosslink the CD150 molecules on T cells (Cocks et al., 1995 and Aversa et al., 1997). In contrast, we have used T cell stimulator cells expressing its natural ligand CD150, to assess the role of CD150–CD150 interaction in the activation of T cells. Our results, which suggest that CD150 does not function as a classical T cell costimulatory molecule, underline the importance of using natural ligands to study the functional consequences of receptor–ligand pairs implicated in T cell activation processes. The homophilic interaction of CD150 is of particular low affinity (Kd 200 mM; (Chattopadhyay et al., 2009)), which might explain the different outcome of our experiments compared to studies that used antibodies.