Blocking of the B7-CD28 pathway increases the capacity of FasL+ (CD95L+) dendritic cells to kill alloactivated T cells.

Dendritic cells (DC) are antigen presenting cells of hemopoietic origin, uniquely well-equipped to activate naive T cells. 1 Evidence also exists however, for DC tolerogenicity.2 During primary activation, mature T cells change from an activation-induced cell death (AICD) -resistant to an AICD-sensitive phenotype.3 The complete molecular basis for this transition remains to be determined, but CD95 (Fas/ Apo-l) and CD95L (Fas ligand; FasL) appear to play an important role in the homeostatic regulation of T cell responses.4 It seems that CD95L can mediate opposite effects (T cell activation or apoptosis) depending on the state of activation of the responding T cells. Previously, we have shown that mouse bone marrow (BM)-derived DC progenitors deficient in expression of cell surface costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are capable of inducing alloantigen-specific T cell hyporesponsiveness$ and prolonging allograft survival.6 Others have shown recently that a major subpopulation of freshly-isolated mouse lymphoid tissue DC is FasL\ and can induce apoptosis in allogeneic T cells.7 In the course of studies on DC propagated in vitro from mouse BM, we observed that these cells expressed Fas L. Our aim was to determine whether these cells could induce T cell apoptosis and whether costimulatory molecule expression could affect this activity.