Initiation of the Autologous Mixed Lymphocyte Reaction Requires the Expression of Costimulatory Molecules B7-1 and B7-2 on Human Peripheral Blood Dendritic Cells

Abstract

The human autologous mixed lymphocyte reaction (AMLR) consists of a proliferative response of primarily CD4+ T lymphocytes stimulated by autologous non-T cells expressing class II MHC-encoded gene products and is thought to represent a self-recognitive mechanism that might be important in regulating the cellular interactions involved in the generation of normal immune responses. To further define appropriate stimulator cell populations, as well as the molecular mechanism responsible for the initiation of AMLR, we compared the T cell-stimulatory capacity of highly purified populations of peripheral blood dendritic cells (DCs) and monocytes (Mos) under serum-free conditions, thus carefully avoiding the presence of xenogeneic Ags. Whereas both freshly isolated Mos and DCs were found to be poor stimulators of autologous T cell proliferation, preactivation of DCs, but not of Mos, for 48 h with granulocyte-macrophage CSF led to a 113-fold increase in DC stimulatory capacity. AMLR was inhibited by mAbs against HLA-DR and CD4 molecules, and, in addition, showed a higher dependence on the granulocyte-macrophage CSF-induced up-regulation and/or de novo expression of the costimulatory molecules B7-2 and, in particular, B7-1 as compared with an Ag-specific or allogeneic MLR. Thus, our data suggest that the high density of costimulatory molecules together with MHC class II molecules on competent APCs appear to be the major triggers for the initiation of AMLR.