title: B-cell growth factor-induced and alpha-interferon-inhibited proliferation of hairy cells coincides with modulation of cell surface antigens.
abstract: alpha-Interferon (IFN-alpha) induced unique ultrastructural alterations in peripheral blood and splenic hairy cell leukemia (HCL) cells (14 of 20 cases) treated in vitro. To further investigate the effects of B-cell growth factor (BCGF) and IFN-alpha on target hairy cells (HCs), we utilized immunogold labeling in conjunction with scanning electron microscopy. This methodology, in contrast to other immunological methods, facilitated direct view of the expression, density, and rearrangement of selected antigens/receptors on individual cells before and after BCGF or IFN-alpha treatment. In addition to inducing proliferation of HCL cells, BCGF enhanced the expression of interleukin 2 receptors (CD25; T-activated cell antigen) with no change in the expression of class I and class II human leukocyte antigen. On the other hand, IFN-alpha did not exert a noticeable proliferative effect on HCL cells but rather inhibited the proliferation of BCGF-treated cells. In addition, IFN-alpha treatment revealed an enhanced expression of class I (4 of 9) and class II (12 of 15) human leukocyte antigen on target HCs. Two-day exposure of HCs to IFN-alpha resulted in enhanced expression of CD25 (11 of 14), whereas a decrease in CD25 expression was recorded in 4 of 5 cases treated with IFN-alpha for 3 days. Also, no significant change in the expression of two other HCL-related surface antigens, CD22 (S-HCL-1; Leu-14) and CD11c(S-HCL-3; Leu-M5), was recorded following up to 3 days of IFN-alpha or BCGF treatment. However, a 5-day exposure to IFN-alpha resulted in a significant decrease in expression of CD11c on treated HCs. Finally, the IFN-alpha-induced immunoultrastructural changes in target HCs were primarily encountered in cells from HCL cases classified as responders to in vivo IFN-alpha therapy. Our data add support to the concept that the effect of IFN-alpha in HCL is mediated by impairment of the response to B-cell growth factors and induction of further differentiation of the target cells.
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Illinois 60637.
authors.forename: H
authors.initials: H
authors.lastname: Gamliel
authors.forename: B H
authors.initials: BH
authors.lastname: Brownstein
authors.forename: D
authors.initials: D
authors.lastname: Gurfel
authors.forename: S H
authors.initials: SH
authors.lastname: Wu
authors.forename: M C
authors.initials: MC
authors.lastname: Rosner
authors.forename: H M
authors.initials: HM
authors.lastname: Golomb
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006680:HLA Antigens; D007370:Interferon Type I; D015375:Receptors, Interleukin-2; D015847:Interleukin-4