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P Mongini, S Seremetis, C Blessinger, S Rudich, R Winchester and M Brunda
Department of Rheumatic Diseases, Hospital for Joint Diseases, New York
University School of Medicine, NY 10003.
A hairy cell leukemia population was used as a clonal model for studying
the direct immunomodulatory effects of recombinant interferon- alpha A
(rIFN-alpha A) and rIFN-gamma on human B-cell proliferation. The leukemic
cell population KON was notably quiescent when incubated in medium alone
but was induced to significant in vitro DNA synthesis when cultured with
any of four activators of human B cells: anti-IgM antibody, Staphylococcus
aureus cells (SAC), phorbol myristate acetate (PMA), or B-cell growth
factor (BCGF). While both rIFN-gamma and rIFN- alpha A exhibited
suppressive effects on these responses, their inhibitory patterns were
distinct and reciprocal. Thus, rIFN-gamma exclusively suppressed
anti-IgM-and SAC-induced leukemic DNA synthesis, and rIFN-alpha A
significantly suppressed only PMA- and BCGF-induced DNA synthesis. The
effects of the rIFN preparations were ablated in the presence of IFN
type-specific monoclonal antibodies. Kinetic analyses and pulsing studies
revealed that inhibition was most notable when cells were exposed
concomitantly to IFN and the activating ligand. That the diverse effects of
IFN-gamma and IFN-alpha A are manifested on a single B-cell clone was
confirmed by Southern blot analysis of restriction enzyme-digested KON cell
DNA with a JH-specific probe. These studies suggest that the therapeutic
potential of the two types of IFN may be influenced by the nature of the
extracellular ligands in the leukemic mileau that promote leukemic clonal
expansion.
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| Copyright © 1988 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||