The proliferative response of T cells to Aspergillus antigen requires prior presentation on dendritic cells

Abstract

Dendritic cells (DC) are the most powerful antigen presenting cells that induce and maintain primary immune response. The present study confirms and extends the evidence that the proliferative response of T lymphocytes to Aspergillus antigen requires prior presentation on DC. Adherent blood monocytes (Mo) from healthy subjects were treated for 5 days with GM-CSF and IL-4 to generate immature DC and with IL-1beta, IL-6, tumor TNF-alpha and PGE2 for 2 days to generate matured DC and pulsed with Aspergillus antigen immediately prior to maturation. The Aspergillus pulsed DC demonstrated the typical morphology, cytoplasmic projections and surface markers of mature DC. Lymphocyte proliferation in response to soluble Aspergillus crude extract was compared with that presented by ex vivo generated autologous DC. The Aspergillus crude extract demonstrated marked toxic effect on peripheral blood mononuclear cells (PBMC) at concentrations started from 25 microg/ml and failed to initiate lymphocyte proliferative response. In contrast Aspergillus-specific T cell proliferation was demonstrated when cocultured with autologous Aspergillus-pulsed, Mo-derived DC and the culture supernatant showed marked IFN-gamma secretion. In conclusion, this study pointed out that the proliferative Th1 responses to Aspergillus requires prior presentation on DC.