B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy

N Selenko-Gebauer, O Majdic, A Szekeres… - The Journal of …, 2003 - journals.aai.org
N Selenko-Gebauer, O Majdic, A Szekeres, G Höfler, E Guthann, U Korthäuer…
The Journal of Immunology, 2003journals.aai.org
In an effort to identify immunoregulatory molecules on dendritic cells (DC), we generated
and screened for mAbs capable of modulating the T cell stimulatory function of DC. A
particularly interesting mAb was mAb DF272. It recognizes monocyte-derived DC, but not
blood monocytes or lymphocytes, and has profound immunomodulatory effects on DC.
Treatment of DC with intact IgG or Fab of mAb DF272 enhanced their T cell stimulatory
capacity. This effect on DC was accompanied by neither an up-regulation of costimulatory …
Abstract
In an effort to identify immunoregulatory molecules on dendritic cells (DC), we generated and screened for mAbs capable of modulating the T cell stimulatory function of DC. A particularly interesting mAb was mAb DF272. It recognizes monocyte-derived DC, but not blood monocytes or lymphocytes, and has profound immunomodulatory effects on DC. Treatment of DC with intact IgG or Fab of mAb DF272 enhanced their T cell stimulatory capacity. This effect on DC was accompanied by neither an up-regulation of costimulatory molecules such as B7. 1 (CD80), B7. 2 (CD86), and MHC class II molecules nor by an induction of cytokine production, including IL-1, TNF-α, IL-10, and IL-12. Moreover, the well-established inhibitory function of IL-10-treated DC could be reverted with mAb DF272. Even T cells, anergized because of stimulation with IL-10-treated DC, could be reactivated and induced to proliferate upon stimulation with mAb DF272-treated DC. Furthermore, mAb DF272-treated DC favored the induction of a type-1 cytokine response in T cells and inhibited IL-10 production. By using a retrovirus-based cDNA expression library generated from DC, we cloned and sequenced the mAb DF272-defined cell surface receptor and could demonstrate that it is identical with B7-H1 (programmed death-1 ligand), a recently identified new member of the B7 family of costimulatory molecules. Our results thus demonstrate that the mAb DF272-defined surface molecule B7-H1 represents a unique receptor structure on DC that might play a role in the induction and maintenance of T cell anergy.
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