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 IFNalpha 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 IFNalpha 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. These findings may indicate allelic differences in regulatory mechanisms of HLA class I antigen expression possibly influencing T-cell recognition in immune responses.