Blocking of the B7-CD28 Pathway Increases the Capacity of FasL⁺ (CD95L⁺) Dendritic Cells to Kill Alloactivated T Cells

Abstract

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-1) 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 hyporesponsiveness⁵ 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.