Interferon-α/β,Pentoxifylline,and Caffeine Synergize with Interferon-γ to Induce Major Histocompatibility Complex Class I Expression on a Constitutively Class I-Negative Murine Tumor Cell Line

Abstract

The constitutively class I-negative tumor cell line, Kgv, expresses H-2D^k in response to interferon-γ (IFN-γ), but not in response to IFN-α/β, tumor necrosis factor, or lymphotoxin. H-2D^k expression was not induced on Kgv cells by the methylxanthines, pentoxifylline (PTX) and caffeine, which modulate class I expression on cells that constitutively express class I molecules. Treatment of Kgv cells with either IFN-α/β, PTX, caffeine, or dibutyryl cAMP and a concentration of IFN-γ insufficient by itself to induce D^k expression resulted in the induction of D^k expression. Since PTX and caffeine are cAMP-specific phosphodiesterase inhibitors, it is possible that the effects of PTX, caffeine, and dibutyryl cAMP involve a cAMP-dependent mechanism. We conclude that concentrations of IFN-γ insufficient to induce D^k expression on Kgv cells may be capable of rendering the D ^k gene responsive to signals that, in the absence of IFN-γ treatment, have no effect on D^k expression.