Interferon-beta induces selective enhancement of antigen-specific T cell responses.
Interferon-beta (IFN-beta) inhibits mitogen-induced T cell responses, in part through downregulation of interleukin-12 (IL-12) or upregulation of IL-10. We have reexamined these findings using ragweed (RW) stimulated or tetanus toxoid (TT)-stimulated human peripheral blood mononuclear cells (PBMC) and nontransformed, antigen-specific, human Th0, Th1, and Th2 clones. IFN-beta induced concentration-dependent inhibition of phytohemagglutinin (PHA)-stimulated PBMC proliferation and enhancement of RW-stimulated or TTstimulated PBMC proliferation. Monocyte depletion of PBMC isolates resulted in concentration-dependent inhibition of RW-driven or TT-driven proliferation by IFN-beta. This response was unaltered by the addition of either exogenous recombinant human IL-12 (rHuIL-12) or saturating concentrations of anti-IL-10. 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 clones stimulated in the presence of antigen and autologous, irradiated PBMC displayed concentration-dependent inhibition of proliferation in the presence of IFN-beta that was unaltered by the addition of either exogenous rHuIL-12 or a saturating concentration of anti-IL-10. Finally, whereas IFN-beta inhibited 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 immunomodulatory rather than an antiproliferative/immunosuppressive cytokine.
Pacocha
S E
SE
Johns Hopkins University School of Medicine, Department of Internal Medicine, Baltimore, MD 21224, USA.
Oriente
A
A
Lichtenstein
L M
LM
Huang
S K
SK
Essayan
D M
DM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008934:Mitogens / Q000276:immunology
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D008934:Mitogens; D016899:Interferon-beta