Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells

Abstract

Utilizing somatic cell hybridization, we have developed a monoclonal antibody that interacts only with cells of the monocyte/macrophage (M∅) line and not with other myeloid or lymphoid cells. This antibody detects a 120,000-dalton determinant present on 37±2.8% of the peripheral blood M∅ from several (HLA-DR)-disparate individuals and only depicts a subpopulation (~30%) of HLA-DR bearing M∅ from any single subjects. Cytolytic removal of this subpopulation of HLA-DR bearing cells markedly diminishes antigen-induced T cell reactivity, a deficiency that can be reconstituted with autologous M∅ but not with either their soluble products containing lymphocyte-activating factor or with intact HLA-DR disparatate M∅. Whereas M∅ bearing both the 120,000-dalton determinant and HLA-DR serve as effective stimulators for autologous mixed lymphocyte reactions. M∅ bearing only HLA-DR determinants do not. However, this latter population of M∅ can stimulate proliferation among alloreactive T cells. These studies indicate that the Mac-120 monoclonal antibody detects a subpopulation of HLA-DR-bearing M∅ that is required for the genetically restricted presentation of conventional antigen to reactive T cells. Within the M∅ population, these Mac-120+ cells constitute the most effective stimulators for autologous mixed lymphocyte reactions.