Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations.
Highly purified natural human interferon-alpha (IFN-alpha) inhibited in a dose-dependent manner the proliferation of human peripheral blood lymphocytes (PBL) stimulated with T-cell mitogen concanavalin A (Con A) or with interleukin-2 (IL-2). Contrary to this inhibitory effect, IFN-alpha at the same concentrations significantly increased proliferation of PBL stimulated with B-cell mitogen bacterial lipopolysaccharide (LPS) or with IL-3, and even spontaneous proliferation of PBL was enhanced by IFN-alpha. Proliferation of Con A-stimulated PBL depleted of CD8+ cells was sensitive to the inhibitory action of IFN-alpha, while proliferation of the Con A-stimulated CD4+ cell-depleted PBL was not affected by IFN-alpha. The inhibitory effect of IFN-alpha on PBL proliferation was due to neither inhibition of IL-2 receptor (IL-2R) expression, activation of suppressor cells, nor inhibition of lymphokine production. Rather, IFN-alpha augmented production of IL-1 and IL-2 by PBL. These results show that the suppressive effect of natural IFN-alpha on Con A-induced proliferation of PBL is due to a direct growth-inhibitory effect on CD4+ T cells, and that IFN-alpha simultaneously augments production of lymphokines. This could in turn lead to the increased proliferation of IFN-alpha-resistant cell populations.
Holán
V
V
Fujisaki Cell Center, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
Nakamura
S
S
Minowada
J
J
D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016898:Interferon-alpha; D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D003208:Concanavalin A