EFFECT OF EXOGENOUS CYTOKINES ON THE INHIBITION OF MACROPHAGE-INDUCED, ANTIGEN-SPECIFIC T-CELL PROLIFERATION BY POLY(I-C)

We have previously demonstrated that IFN-α/β, poly(I:C) (an inducer of IFN-α/β), or IFN-γ can inhibit the ability of KLH-pulsed peritoneal macrophages (Mφ) to induce the proliferation of syngeneic, KLH-immune T lymphocytes from CBA/J mice. In this study we investigated whether the mechanism by which poly(I:C) inhibits Mφ-induced, antigen-specific T cell proliferation involved decreased cytokine production by poly(I:C) treated KLH-pulsed Mφ or by T cells cultured with these Mφ. The production of IL-2 by T cells cultured with poly(I:C)-treated, KLH-pulsed Mφ was decreased by 80%; however, addition of exogenous rIL-2 could not restore proliferation. Although IL-1 production by poly(I:C)-treated Mφ was comparable to the level produced by saline-treated, KLH-pulsed Mφ controls, addition of exogenous rIL-1 was still examined to explore the possibility that a greater amount of IL-1 may be needed to induce T cell proliferation with poly(I:C)-treated, KLH-pulsed Mφ. Increasing concentrations of rIL-1 alone or with rIL-6 did not abrogate the inhibition of Mφ-induced, antigen-specific T cell proliferation by poly(I:C). Interestingly, the addition of combinations of IL-1 and IL-6 increased the proliferation of T cells in response to KLH presented by either saline- or poly(I:C)-treated Mφ. The effect of the combination of rIL-1 and rIL-6 was synergistic in that addition of either monokine alone had no effect on T cell proliferation. These results suggest that although poly(I:C)-induced inhibition of T cell proliferation is not due to insufficient quantities of IL-1, IL-2, or IL-6, a combination of IL-1 and IL-6 can augment proliferation of freshly isolated T cells in response to antigen presented by freshly isolated accessory cells. © 1992.