Modulation of the expression of major histocompatibility antigens on splenic hairy cells--differential effect upon in vitro treatment with alpha-2b-interferon, gamma-interferon, and interleukin-2.
The mechanism of action responsible for the beneficial effect of alpha-interferon (alpha-IFN) in patients with hairy cell leukemia (HCL) is still unknown. Direct antineoplastic and immunomodulating effects on both the host immune system and the hairy cells themselves have been implicated. To evaluate whether lymphokines have any regulatory effect on antigens of the major histocompatibility complex (MHC) on hairy cells and whether this corresponds to prognostic clinical parameters, we studied splenic hairy cells from ten previously untreated patients. The samples were incubated with recombinant human alpha-IFN, gamma-IFN (gamma-IFN), and interleukin-2 (IL-2). In an indirect staining procedure, cells were labeled with monoclonal antibodies (MoAb) to HLA ABC and HLA DR surface structures and subjected to cytofluorimetric analysis. Results concerning the expression of MHC class I and HLA DR antigens were mixed for incubation of hairy cells with gamma-IFN and IL-2, whereas alpha-IFN had a distinct effect on HLA DR antigen expression. alpha-IFN strongly enhanced the intensity of staining with HLA DR MoAb in six patients, and it increased the percentage of MoAb-positive cells in five of these samples. In contrast, the staining intensity in samples from four patients was reduced considerably on alpha-IFN treatment. In this group, two samples showed a sharp alpha-IFN-induced decrease in the number of HLA DR MoAb-positive cells from originally high values, and in one sample the very low percentage of positive cells was unaffected by alpha-IFN exposure. These two groups of patients whose hairy cells displayed contrasting HLA DR expression on incubation with alpha-IFN in vitro, were found to differ in their subsequent clinical course.
D000818:Animals; D000911:Antibodies, Monoclonal; D006680:HLA Antigens / Q000032:analysis*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000276:immunology*; D007958:Leukocyte Count; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000473:pathology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D007370:Interferon Type I; D007376:Interleukin-2; D007371:Interferon-gamma