Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication.

Abstract

Two recent studies (1, 2) have identified cells in human blood that fully resemble the dendritic cells described previously in mice and rats (3). Among other similarities, the human equivalent is Ia positive and Fc receptor negative, occurs in trace numbers (<1% of blood mononuclear cells), and acts as a potent stimulator of T cell proliferation in vitro. For example, preparations enriched in dendritic cells are 10-100 times more active than monocytes or lymphocytes in stimulating the syngeneic and allogeneic mixed leukocyte reactions (MLR) ~ as well as oxidative mitogenesis--the proliferation of periodate-modified T cells (1, 2). Therefore the prevailing concept that monocytes are the principal accessory cells in man must be reexamined.Monoclonal antibodies that distinguish macrophages from dendritic cells provide new probes for accessory or stimulator cells in the immune response. Selective depletion of murine dendritic cells, with specific antibody and complement, decreases accessory function dramatically (4-6). In man, antidendritic cell antibodies are not available, but alternative and useful reagents have been obtained. For example, 3C10 and 1 D9 are related antimacrophage antibodies that do not react with dendritic cells, while 9.3F10 is an anti-HLA class II reagent (7) that reacts with both cell types. In this paper, we use these monoclonals to study the requirements for T cell proliferation. T cell growth is severely reduced when accessory cells are depleted with 9.3F10 and complement, or when an Fab fragment of 9.3F10 is added to the culture. Positive and negative monocyte selection experiments, with the fluorescence-activated cell sorter and with complement-mediated cytolysis, indicate that monocytes contribute little if at all to accessory function. In contrast, highly enriched and monocyte-depleted dendritic cells are potent stimulators of the syngeneic and allogeneic MLR and the response to soluble tetanus toxoid. Monocytes and dendritic cells express similar levels of Ia antigens, however, indicating that class II products need to be expressed on dendritic cells to induce several T cell-proliferative responses in man.

Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues.

“…Either an undetectable number of DC entered these sites, thought to be important for differentiation of cells of the DC lineage, or another precursor in blood (for which there is as yet no evidence) gives rise to the Langerhans' cells and other DC-like cells of nonlymphoid tissues. DC isolated from peripheral blood of humans are indistinguishable in phenotype and function from those isolated from spleens and tonsils (15,16). Presumably, they also exist in the peripheral blood of rodents, but for practical reasons they cannot be isolated .…”

Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes

“…The PBMC-derived DCs were irradiated at 30 Gy with an IBL 437C irradiator (CIS Bio International, Gif-SurYvette Cedex, France). This dose of radiation blocks cell proliferation, but keeps the secretory responses intact [19,20]. The lymphocytes and irradiated DCs (10 : 1 ratio) were placed in a 24-well culture plates (Corning, NY, USA) and cultured with or without the anti-IL-12 neutralizing antibody C8´6 (85 mg/ml) (Genzyme, Cambridge, MA, USA).…”

Comparison of the Accessory Activity of Murine Peritoneal Cavity Macrophage Derived Dendritic Cells and Peritoneal Cavity Macrophages in a Mixed Lymphocyte Reaction.

“…They are the principal stimulators of primary immune responses [13,26,35,38,39]. In studies of lymphoid DC as potent stimulators of the MLR in mice, Steinman and Whitmer [7] showed that a ratio of just one DC to 50-250 T cells induced a maximal reaction.…”