Donor dependent, interferon-gamma induced HLA-DR expression on human neutrophils in vivo.
Neutrophils are effector cells of innate immune responses. Stimulated by interferon-gamma (IFN-gamma) to express HLA-DR, neutrophils acquire accessory cell functions for superantigen-mediated T cell activation. In vitro HLA-DR induction on neutrophils varies in a functionally relevant way as levels of MHC class II expression and magnitude of neutrophil induced T cell responses are correlated functions. The aim of this study was to assess whether IFN-gamma induces HLA-DR on human neutrophils in a donor dependent fashion in vivo and to define regulatory events operative in MHC class II expression of neutrophils. In vivo administration of rhIFN-gamma in 55 patients with renal cell carcinoma resulted in a varying increase of HLA-DR on neutrophils. By setting a cut-off for response at>10% HLA-DR positive neutrophils, HLA-DR responders (51%) were as frequent as nonresponders (49%). In vivo kinetic studies revealed a peak expression of HLA-DR on neutrophils 48 h after rhIFN-gamma application, while nonresponders remained HLA-DR negative over a 72-h period. In vitro IFN-gamma stimulated neutrophils recapitulated the response profiles observed in vivo. No differences in IFN-gamma dependent CD64 and invariant chain expression, and IFN-gamma serum levels were observed among the response subgroups. HLA-DR mRNA was detected in neutrophils from rhIFN-gamma treated responders and nonresponders, HLA-DR protein solely in lysates of responder neutrophils. IFN-gamma stimulated HLA-DR expression on neutrophils is subject to donor dependent variations in vivo, which result from rather post-transcriptional than transcriptional regulation. Due to their abundance in inflammatory reactions heterogeneous HLA-DR expression by neutrophils could determine the outcome of superantigen-driven diseases.
Reinisch
W
W
Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, Centre of Molecular Medicine of the Austrian Academy of Sciences, University of Vienna, Vienna, Austria. walter.reinisch@akh-wien.ac.at
Lichtenberger
C
C
Steger
G
G
Tillinger
W
W
Scheiner
O
O
Gangl
A
A
Maurer
D
D
Willheim
M
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D015153:Blotting, Western / Q000379:methods; D002292:Carcinoma, Renal Cell / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007371:Interferon-gamma