Donor dependent, interferon-γinduced HLA-DR expression on human neutrophilsin vivo

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Abstract
Neutrophils are effector cells of innate immune responses. Stimulated by interferon‐γ (IFN‐γ) 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‐γ 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‐γ 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‐γ application, while nonresponders remained HLA‐DR negative over a 72‐h period. In vitro IFN‐γ stimulated neutrophils recapitulated the response profiles observed in vivo. No differences in IFN‐γ dependent CD64 and invariant chain expression, and IFN‐γ serum levels were observed among the response subgroups. HLA‐DR mRNA was detected in neutrophils from rhIFN‐γ treated responders and nonresponders, HLA‐DR protein solely in lysates of responder neutrophils. IFN‐γ 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.