Differential regulation of human leukocyte antigen class I genes by interferon in vivo and in vitro.
Modulation of human leukocyte antigen (HLA) class I antigens on peripheral blood lymphocytes, monocytes, and hematopoietic precursors during interferon-alpha (IFN-alpha) therapy was investigated in 18 patients with myeloproliferative syndrome. After 1 month of IFN-alpha therapy, an increased number of monocytes and hematopoietic precursor cells but not of lymphocytes expressed HLA-DQ antigens. In addition, a strong induction of HLA class I antigens was found on both hematopoietic progenitors and normal peripheral blood mononuclear cells. By daily injections of IFN in the first month of therapy, stimulation continuously increased, suggesting a major effect of IFN alpha on hematopoietic progenitors with sustained enhanced expression of HLA class I antigens during differentiation of myelomonocytic cells. HLA class I antigen expression was consistently augmented by IFN alpha in all patients irrespective of their hematologic response. Differential in vivo regulation of HLA class I antigens by IFN was confirmed by comparison of HLA-A2 with HLA-B antigen expression. In vitro expression of the HLA-B7 and -Bw64 genes had been shown earlier to be significantly more inducible by IFN than the genes coding for several other HLA class I antigens after transfection into mouse L cells. Modification of the 5' ends of the HLA-B7 and HLA-B27 genes before transfection in mouse L cells showed the presence of enhancer sequences responding to IFN treatment in the 5' untranslated region of the HLA-B7 but not of the HLA-B27 gene and suggested the presence of independently acting regulatory mechanisms independent of these enhancers.(ABSTRACT TRUNCATED AT 250 WORDS)
Schmidt
H
H
Med. Universitätsklinik u. Poliklinik, Tübingen, Germany.
Kellermann-Kegreiss
E
E
Steiert
I
I
Walz
J
J
Zinser
R
R
Müller
C A
CA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005805:Genes, MHC Class I / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000628:therapy*
D015703:Antigens, CD; D018952:Antigens, CD34; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha