Article

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

Institute of Immunology, University of Vienna Medical School, Vienna, Austria.
The Journal of Immunology (impact factor: 5.79). 05/2003; 170(7):3637-44.
Source: PubMed

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-alpha, 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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Keywords

blood monocytes
 
cytokine production
 
dendritic cells
 
identified new member
 
IL-10-treated DC
 
immunoregulatory molecules
 
inhibited IL-10 production
 
mAb DF272-defined cell surface receptor
 
mAb DF272-defined surface molecule B7-H1
 
mAb DF272-treated DC
 
monocyte-derived DC
 
profound immunomodulatory effects
 
retrovirus-based cDNA expression library
 
T cell anergy
 
T cell stimulatory capacity
 
T cell stimulatory function
 
T cells
 
type-1 cytokine response
 
unique receptor structure
 
well-established inhibitory function