INITIATION OF THE AUTOLOGOUS MIXED LYMPHOCYTE-REACTION REQUIRES THE EXPRESSION OF COSTIMULATORY MOLECULES B7-1 AND B7-2 ON HUMAN PERIPHERAL-BLOOD DENDRITIC CELLS

The human autologous mixed lymphocyte reaction (AMLR) consists of a pr oliferative response of primarily CD4(+) T lymphocytes stimulated by a utologous non-T cells expressing class II MHC-encoded gene products an d is thought to represent a self-recognitive mechanism that might be i mportant in regulating the cellular interactions involved in the gener ation of normal immune responses, To further define appropriate stimul ator cell populations, as well as the molecular mechanism responsible for the initiation of AMLR, we compared the T cell-stimulatory capacit y of highly purified populations of peripheral blood dendritic cells ( DCs) and monocytes (Mos) under serum-free conditions, thus carefully a voiding the presence of xenogeneic Ags, Whereas both freshly isolated Mos and DCs were found to be poor stimulators of autologous T cell pro liferation, preactivation of DCs, but not of Mos, for 48 h with granul ocyte-macrophage CSF led to a 113-fold increase in DC stimulatory capa city. AMLR was inhibited by mAbs against HLA-DR and CD4 molecules, and , in addition, showed a higher dependence on the granulocyte-macrophag e CSF-induced up-regulation and/or de novo expression of the costimula tory molecules B7-2 and, in particular, B7-1 as compared with an Ag-sp ecific or allogeneic MLR. Thus, our data suggest that the high density of costimulatory molecules together with MHC class II molecules on co mpetent APCs appear to be the major triggers for the initiation of AML R.