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-alpha/beta, poly(I:C) (an inducer of IFN-alpha/beta), or IFN-gamma can inhibit the ability of KLH-pulsed peritoneal macrophages (M phi) 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 M phi-induced, antigen-specific T cell proliferation involved decreased cytokine production by poly(I:C) treated KLH-pulsed M phi or by T cells cultured with these M phi. The production of IL-2 by T cells cultured with poly(I:C)-treated, KLH-pulsed M phi was decreased by 80%; however, addition of exogenous rIL-2 could not restore proliferation. Although IL-1 production by poly(I:C)-treated M phi was comparable to the level produced by saline-treated, KLH-pulsed M phi 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 M phi. Increasing concentrations of rIL-1 alone or with rIL-6 did not abrogate the inhibition of M phi-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 M phi. 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.
Kirschmann
D A
DA
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Murasko
D M
DM
D000818:Animals; D006433:Hemocyanins / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011070:Poly I-C / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D006433:Hemocyanins; D011070:Poly I-C