Human dendritic cells express functional interleukin-7.

ABSTRACT

Interleukin-7 (IL-7) supports the proliferation of mature T lymphocytes, however, the cellular source of IL-7 for T lymphocyte activation has not been well established. We therefore investigated whether human peripheral blood dendritic cells (DC) produce IL-7 as a contribution towards T lymphocyte activation. Human CMRF-44+/CD14-/CD19- low density DC, purified after overnight tissue culture, contained IL-7 transcripts, detected by direct cell reverse transcription-polymerase chain reaction. Intracytoplasmic staining confirmed IL-7 protein in at least a subpopulation of cultured low density DC. In contrast, resting/immature DC, isolated directly by immunodepletion of lineage marker positive cells, contained no IL-7 mRNA. Thus, the expression of IL-7 by DC follows the pattern described previously for CD80, CD86 and CD40. However, tissue culture of purified resting/immature DC, in contrast to CD80, CD86 and CD40, failed to induce IL-7 transcripts. The functional importance of DC IL-7 expression was demonstrated in an allogeneic mixed leukocyte reaction (MLR). Neutralising mAb to IL-7 significantly inhibited T lymphocyte proliferation when low DC numbers were used, but at higher stimulator numbers, anti-IL-7 mAb failed to inhibit an allogeneic MLR. This suggests, that when DC are in excess, other co-stimulatory pathways can compensate for the lack of IL-7. Addition of IL-7 to a MLR caused a significant increase in the proliferative response stimulated by monocytes and B lymphocytes but not by DC. These data support the concept of an initial phase of antigen uptake by DC followed by the optimisation of DC co-stimulatory potential. The co-stimulatory repertoire expressed, including IL-7, may be regulated by exogenous stimuli, thereby ensuring DC flexibility in mounting a response appropriate to the environmental changes.