Glucocorticoids hamper the ex vivo maturation of lung dendritic cells fromtheir low autofluorescent precursors in the human bronchoalveolar lavage: decreases in allostimulatory capacity and expression of CD80 and CD86
Gt. Verhoeven et al., Glucocorticoids hamper the ex vivo maturation of lung dendritic cells fromtheir low autofluorescent precursors in the human bronchoalveolar lavage: decreases in allostimulatory capacity and expression of CD80 and CD86, CLIN EXP IM, 122(2), 2000, pp. 232-240
Dendritic cells (DCs) were prepared from human bronchoalveolar lavage (BAL)
cells. We previously reported that, in particular, the CD1a fraction of th
e low autofluorescent (LAF) cells contains the precursors for DCs: after ov
ernight culture, 40% of the LAF cells change into functionally and phenotyp
ically prototypic dendritic/veiled cells. There are, as yet, no data on the
modulatory effects of glucocorticoids (GC) on the maturation and function
of such DCs isolated from the human lung. Functional tests (allogeneic mixe
d lymphocyte reaction: allo-MLR) were therefore performed with CD1a(+) LAF
cells at different stimulator-to-T-cell ratios and after preincubation with
different dexamethasone (DEX) concentrations. DEX caused suppression of th
e T-cell stimulatory capacity of CD1a(+) LAF cells, which was dose-dependen
t, and more evident at the higher stimulator-to-T-cell ratios. Here, we als
o show that CD80 and CD86 are normally expressed at low levels on CD1a(+) L
AF cell-derived DCs compared to other DC populations. This low-level expres
sion of costimulatory molecules is discussed here in relation to the previo
usly reported low-level expression of CD80 (and CD86) on lung DCs in experi
mental animals. This appears to play a role in a predominant Th2 cell stimu
lating potential of DC from the lung environment. DEX exposure of CD1a(+) L
AF cells prevented the upregulation of even this low-level expression of CD
80 and CD86. The veiled/dendritic morphology and the expression of other re
levant cell surface markers and adhesion molecules was not affected by DEX
exposure. It is concluded that DEX hampers the maturation of CD1a(+) LAF ce
lls into active lung DCs.