Mesenchymal stem cells (MSCs), isolated from adult human bone marrow, have immunomodulatory properties. The functional outcomes of MSCs-CTL interactions remain poorly characterized. In this study, we demonstrate that MSCs remain resistant to CTL lysis, even after pulsing with the specific synthetic peptide at high concentrations, in spite of surface expression of the relevant MHC class I allele. MSCs were also much less sensitive to lysis by an allo-specific CTL clone as compared with HLA-matched lymphoblastoid cell lines. MSCs induced CD25 up-regulation, albeit at relatively low levels, and were unable to induce CD3 or CD8 down-regulation at the surface of CTLs. MSCs also failed to induce IFN-gamma and TNF-alpha production by the CTLs. Furthermore, peptide-pulsed MSCs were inefficient in stimulating tyrosine phosphorylation in specific CTLs. Our results demonstrate that MSCs induce only an abortive activation program in fully differentiated, effector CTLs, which does not involve activation of major CTL effector functions. These data may have important implications for the development of therapeutic strategies based on administration of in vitro-expanded MSCs.