HUMAN BLOOD CONTAINS 2 SUBSETS OF DENDRITIC CELLS, ONE IMMUNOLOGICALLY MATURE AND THE OTHER IMMATURE

Two subsets of dendritic cells, differing in T-cell stimulatory functi on, have been purified directly from human blood. Both subsets are pos itive for major histocompatibility complex (MHC) class II expression a nd negative for lineage-specific antigens (e.g. CD3, CD14, CD16, CD19 negative), but are separated by exploiting differences in expression o f the beta(2)-integrin, CD11c. The CD11c-negative subset is functional ly immature, requiring monocyte-derived cytokines to develop into typi cal dendritic cells. The CD11c-positive subset has potent T-cell stimu lating activity and expresses the activation antigen CD45RO, unlike it s immature counterpart. However, these mature cells only develop typic al dendritic morphology and high levels of MHC proteins and adhesins a fter a period of culture independent of exogenous cytokines. Although the freshly isolated mature dendritic cells resemble monocytes in cyto spin preparations, the former lack CD14 and have a much stronger prima ry T-cell stimulatory capacity. We hypothesize that the CD11c-negative immature cells are marrow-derived precursors to tissue dendritic cell s, such as epidermal Langerhans' cells, while the CD11c-positive cells are derived from tissues where they have been activated by antigen, a nd are en route to the spleen or lymph nodes to stimulate T-cell respo nses there.