HUMAN DENDRITIC CELLS EXPRESS FUNCTIONAL INTERLEUKIN-7

Interleukin-7 (IL-7) supports the proliferation of mature T lymphocyte s, however, the cellular source of IL-7 for T lymphocyte activation ha s not been well established. We therefore investigated whether human p eripheral blood dendritic cells (DC) produce IL-7 as a contribution to wards T lymphocyte activation. Human CMRF-44(+)/CD14(-)/CD19(-) low de nsity DC, purified after overnight tissue culture, contained IL-7 tran scripts, detected by direct cell reverse transcription-polymerase chai n reaction. Intracytoplasmic staining confirmed IL-7 protein in at lea st a subpopulation of cultured low density DC. In contrast, resting/im mature DC, isolated directly by immunodepletion of lineage marker posi tive cells, contained no IL-7 mRNA. Thus, the expression of IL-7 by DC follows the pattern described previously for CD80, CD86 and CD40. How ever, tissue culture of purified resting/immature DC, in contrast to C D80, CD86 and CD40, failed to induce IL-7 transcripts. The functional importance of DC IL-7 expression was demonstrated in an allogeneic mix ed leukocyte reaction (MLR). Neutralising mAb to IL-7 significantly in hibited T lymphocyte proliferation when low DC numbers were used, but at higher stimulator numbers, anti-IL-7 mAb failed to inhibit an allog eneic MLR. This suggests, that when DC are in excess, other co-stimula tory pathways can compensate for the lack of IL-7. Addition of IL-7 to a MLR caused a significant increase in the proliferative response sti mulated by monocytes and B lymphocytes but not by DC. These data suppo rt the concept of an initial phase of antigen uptake by DC followed by the optimisation of DC co-stimulatory potential. The co-stimulatory r epertoire expressed, including IL-7, may be regulated by exogenous sti muli, thereby ensuring DC flexibility in mounting a response appropria te to the environmental changes.