Characteristics of antigen‐independent and antigen‐dependent interaction of dendritic cells with CD4+ T cells

Dendritic cells (DC) are the main antigen‐presenting cells for the initiation of primary T cell‐mediated immune responses. In the first stage of activation, T cells bind to DC in an antigen‐independent manner. We studied the adhesion characteristics of human CD4+ T cells to DC generated from CD34+ hematopoietic progenitors following 12 to 13 days of culture in the presence of granulo‐cyte/macrophage colony‐stimulating factor and tumor necrosis factor‐α. A majority of these cells had the morphology, phenotype and functions of DC. CD4+ T/DC adhesion was measured by means of fluorescence microscopy and flow cytometry. Four independent receptor/ligand pathways, LFA‐1/ICAM, ICAM/LFA‐1, CD2/LFA‐3 and CD28/CD80, were involved in the transient adhesion of DC to CD4+ T cells in antigen‐independent and specific alloantigen‐dependent situations, as shown by blocking experiments using monoclonal antibodies. The antibodies also blocked a primary mixed lymphocyte reaction (MLR) in which DC were used as stimulatory cells. Adhesion of alloreactive CD4+ T cells to antigen‐presenting DC was stronger than that of resting CD4+ T cells, while peak adhesion occurred after 5 and 20 min, respectively. The LFA‐1 ligands involved in adhesion of resting CD4 T cells to DC and alloreactive CD4+ T cells to specific DC differed in part, since ICAM‐3 on resting T cells and ICAM‐1 on alloreactive T lymphocytes preferentially bound LFA‐1. Studies of interactions between DC and phorbol ester‐activated T cells expressing the CD40 ligand revealed a fifth independent adhesion pathway, CD40/CD40 ligand. CD4‐mediated regulation of CD4+ T/DC adhesion was suggested by the observation that preincubation of CD4+ T cells and DC individually with anti‐CD4 antibodies inhibited adhesion. In addition, antibodies specific for HLA class II molecules inhibited adhesion when used to pretreat DC but not alloactivated CD4+ T cells.