Interferon-beta induces selective enhancement of antigen-specific T cell responses

Interferon-beta (IFN-beta) inhibits mitogen-induced T cell responses, in pa rt through downregulation of interleukin-12 (IL-12) or upregulation of IL-1 0, We have reexamined these findings using ragweed (RW) stimulated or tetan us toroid (TT)-stimulated human peripheral blood mononuclear cells (PBMC) a nd nontransformed, antigen-specific, human Th0, Th1, and Th2 clones. IFN-be ta induced concentration-dependent inhibition of phytohemagglutinin (PHA)-s timulated PBMC proliferation and enhancement of RW-stimulated or TT-stimula ted PBMC proliferation, Monocyte depletion of PBMC isolates resulted in con centration-dependent inhibition of RW-driven or TT-driven proliferation by IFN-beta, This response was unaltered by the addition of either exogenous r ecombinant human IL-12 (rHuIL-12) or saturating concentrations of anti-IL-1 0. Moreover, addition of exogenous rHuIL-10 to nondepleted RW-driven or TT- driven PBMC cultures did not alter the concentration-dependent enhancement of antigen-driven proliferation induced by IFN-beta, Th0, Th1, and Th2 clon es stimulated in the presence of antigen and autologous, irradiated PBMC di splayed concentration-dependent inhibition of proliferation in the presence of IFN-beta that was unaltered by the addition of either exogenous rHuIL-1 2 or a saturating concentration of anti-IL-10. Finally, whereas IFN-beta in hibited antigen-driven generation of IL-5, IL-12, IL-13, and IFN-gamma, IFN -beta enhanced generation of both IL-4 and IL-10, Thus, IFN-beta induces a selective, IL-10-independent and IL-12-independent upregulation of antigen- specific T cell responses, supporting the role of IFN-beta as an immunomodu latory rather than an antiproliferative/immuno-suppressive cytokine.