Enhancement by Interferon of Membrane HLA Antigens in Patients with Combined Immunodeficiency with Defective HLA Expression

Since interferon is known to enhance HLA A-B expression on lymphocytes from normal donors, we have tested the hypothesis that interferon could reverse the defective membrane expression of HLA antigens observed in some patients with combined immunodeficiency. Leucocytes from four patients with this syndrome, after overnight incubation with preparations of interferon, showed a clear enhancement in the percentage of cells bearing HLA A-B-C and beta 2 microglobulin (but not HLA-DR) antigens as detected by membrane immunofluorescence. Functional HLA-A and B antigens also appeared on patients' T cell blasts treated with interferon, as shown by the ability of these blasts to be destroyed by specific cytotoxic T lymphocytes. Both alpha and beta human interferons were effective. These effects were shown to be mediated by interferon (but not contaminants in our preparations) by the use of specific antiserum to interferon. It is likely that interferon acts on HLA synthesis, since in vitro addition of drugs known to inhibit nucleic acid or protein synthesis completely abolished the enhancing effect of interferon on membrane HLA expression. Interferons can therefore modulate leucocyte HLA expression and synthesis in patients with defective expression of these antigens, a finding which suggests that interferon treatment might be beneficial in this condition.