P. Hauss et al., CHARACTERISTICS OF ANTIGEN-INDEPENDENT AND ANTIGEN-DEPENDENT INTERACTION OF DENDRITIC CELLS WITH CD4(-CELLS() T), European Journal of Immunology, 25(8), 1995, pp. 2285-2294
Dendritic cells (DC) are the main antigen-presenting cells for the ini
tiation of primary T cell-mediated immune responses. In the first stag
e of activation, T cells bind to DC in an antigen-independent manner.
We studied the adhesion characteristics of human CD4(+) T cells to DC
generated from CD34(+) hematopoietic progenitors following 12 to 13 da
ys of culture in the presence of granulocyte/macrophage colony-stimula
ting factor and tumor necrosis factor-alpha. A majority of these cells
had the morphology, phenotype and functions of DC. CD4(+) T/DC adhesi
on was measured by means of fluorescence microscopy and flow cytometry
. Four independent receptor/ligand pathways, LFA-1/ICAM, ICAM/LFA-1, C
D2/LFA-3 and CD28/CD8O, were involved in the transient adhesion of DC
to CD4(+) T cells in antigen-independent and specific alloantigen-depe
ndent situations, as shown by blocking experiments using monoclonal an
tibodies. The antibodies also blocked a primary mixed lymphocyte react
ion (MLR) in which DC were used as stimulatory eels. Adhesion of allor
eactive CD4(+) T cells to antigen-presenting DC was stronger than that
of resting CD4(+) T cells, while peak adhesion occurred after 5 and 2
0 min, respectively. The LFA-1 ligands involved in adhesion of resting
CD4 T cells to DC and alloreactive CD4(+) T cells to specific DC diff
ered in part, since ICAM-3 on resting T cells and ICAM-1 on alloreacti
ve T lymphocytes preferentially bound LFA-1. Studies of interactions b
etween DC and phorbol ester-activated T cells expressing the CD40 liga
nd revealed a fifth independent adhesion pathway, CD40/CD40 ligand. CD
4-mediated regulation of CD4(+) T/DC adhesion was suggested by the obs
ervation that preincubation of CD4(+) T cells and DC individually with
anti-CD4 antibodies inhibited adhesion. In addition, antibodies speci
fic for HLA class II molecules inhibited adhesion when used to pretrea
t DC but not alloactivated CD4(+) T cells.