DENDRITIC CELLS THAT PROCESS AND PRESENT NOMINAL ANTIGENS TO NAIVE T-LYMPHOCYTES ARE DERIVED FROM CD2(+) PRECURSORS

Dendritic cells (DC) are potent APC that, in mature form, can be disti nguished from other mononuclear cells on the basis of their distinct m orphology, absence of lineage markers, and dense expression of MHC and costimulatory molecules. While comparing different DC preparation met hods, we observed that DC derived from cultured PBMC that had been dep leted of CD2(+) cells before culture were functionally distinct from D C derived from PBMC that had not been depleted of CD2(+) cells. Thus, both types of DC stimulated allogeneic T cells to proliferate in the M LR, but only DC derived from CD2(+) precursors could sensitize naive T cells to soluble Ags such as keyhole limpet hemocyanin and HIV gp1 60 glycoprotein. Subsequent studies confirmed the existence of CD2(+) an d CD2(-) DC precursor populations among HLA-DR(bright), lineage-negati ve PBMC. Immediately after their isolation, these populations were mor phologically similar to one another by light and electron microscopy, and neither had substantial Ag-presenting activity. After culture for 24 to 48 h with supernatant from PHA-activated PBMC, both populations developed dendrites, formed clusters with T cells, and stimulated allo geneic T cell responses in the MLR as well as autologous T cell respon ses to tetanus toroid, a recall Ag. However, CD2(+) DC precursors alon e gave rise to APC that presented soluble Ags to naive CD4(+) T cells, a property that could be inhibited by Abs to CD4, CD11a, and CD28 on T cells or CD86 on DC. The expression of CD54 and CD86 on CD2(+) DC pr ecursors was increased markedly after their culture and differentiatio n, while the expression of these molecules on CD2(-) DC precursors was not remarkably changed. These findings reveal the existence of two fu nctionally distinct populations of DC, each derived from a phenotypica lly distinct precursor present in monocyte-depleted peripheral blood.