No abstract

Chronic alcoholism in the absence of liver disease is associated with an increased secretion of inflammatory cytokines by PB DC, whereas ALCAW and ALCET patients show decreased numbers of circulating DC and reduced secretion of these cytokines, respectively.

SUMMARYDendritic cells (DC) represent the most powerful professional antigen-presenting cells (APC) in the immune system. The aim of the present study was to analyse, on a single-cell basis by multiparametric ow cytometry with simultaneous four-colour staining and a two-step acquisition procedure, the immunophenotypic pro®le and cytokine production of DC from 67 normal whole peripheral blood (PB) samples. Two clearly different subsets of HLA-II /lineage À were identi®ed on the basis of their distinct phenotypic characteristics: one DC subset was CD33 strong and CD123 dim (0´16 6 0´06% of the PB nucleated cells and 55´9 6 11´9% of all PB DC) and the other, CD33 dim and CD123 strong (0´12 6 0´04% of PB nucleated cells and 44´53 6 11´5% of all PB DC). Moreover, the former DC subpopulation clearly showed higher expression of the CD13 myeloid-associated antigen, the CD29 and CD58 adhesion molecules, the CD2, CD5 and CD86 costimulatory molecules, the CD32 IgG receptor and the CD11c complement receptor. In addition, these cells showed stronger HLA-DR and HLA-DQ expression and a higher reactivity for the IL-6 receptor a-chain (CD126) and for CD38. In contrast, the CD123 strong /CD33 dim DC showed a stronger reactivity for the CD4 and CD45RA molecules, whereas they did not express the CD58, CD5, CD11c and CD13 antigens. Regarding cytokine production, our results show that while the CD33 strong /CD123 dim DC are able to produce signi®cant amounts of in¯ammatory cytokines, such as IL-1b (97 6 5% of positive cells), IL-6 (96 6 1´1% of positive cells), IL-12 (81´5 6 15´5% of positive cells) and tumour necrosis factor-alpha (TNF-a) (84 6 22´1% of positive cells) as well as chemokines such as IL-8 (99 6 1% of positive cells), the functional ability of the CD123 strong /CD33 dim DC subset to produce cytokines under the same conditions was almost null. Our results therefore clearly show the presence of two distinct subsets of DC in normal human PB, which differ not only in their immunophenotype but also in their functionality, as regards cytokine production.