Defective expression of B7-2 (CD86) on monocytes of dialysis patients correlates to the uremia-associated immune defect.
BACKGROUND
Specific cellular immune reactions in patients with chronic renal failure (CRF) are impaired by a defect of the antigen-presenting cells. To elucidate the molecular background for this defect, we determined the expression of human lymphocyte antigen (HLA)-DR and costimulatory molecules on monocytes of hemodialysis patients.


METHODS
The expression of HLA-DR, B7-1 (CD80), and B7-2 (CD86) molecules was determined on CD14+ monocytes of chronic hemodialysis patients prior to a dialysis session. Mononuclear cells of these patients were cultured, and expression of the respective antigens was determined after in vitro activation by various stimuli. Results were correlated with in vitro proliferation of T cells in a phytohemagglutinin (PHA) assay and the clinical response to a hepatitis B vaccination. All data were compared with healthy controls and patients with CRF who were not on dialysis.


RESULTS
Monocytes of chronic hemodialysis patients but not CRF patients expressed low levels of costimulatory B7-2, while HLA-DR expression was normal. B7-1 was only expressed on activated monocytes, and the expression reached normal levels in hemodialysis patients. Baseline expression of B7-2 highly correlated with the results of T-cell proliferation assays in hemodialysis patients and also with the clinical immune response.


CONCLUSIONS
Impaired expression and up-regulation of B7-2 is an important feature of the cellular immune defect in chronic hemodialysis patients. It leads to reduced costimulation and effector activation of T cells and contributes to a molecular explanation for the impaired response of hemodialysis patients to the hepatitis B vaccination.
Girndt
M
M
Medical Department IV, University of the Saarland, Homburg/Saar, Germany.
Sester
M
M
Sester
U
U
Kaul
H
H
Köhler
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D000954:Antigens, Surface / Q000378:metabolism; D051940:B7-2 Antigen; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014511:Uremia / Q000097:blood* / Q000276:immunology*
D015703:Antigens, CD; D000954:Antigens, Surface; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D000242:Cyclic AMP