Interleukin-2 can prevent and reverse antigen-induced unresponsiveness in cloned human T lymphocytes.
The exposure of human T-cell clones to supra-immunogenic concentrations of peptide antigen in the absence of accessory cells induces antigen-specific unresponsiveness. Using this model we have investigated the ability of cytokines to modulate the induction of, or reversal of, T-cell tolerance. Our findings demonstrate that interleukin-2 (IL-2), but not interferon-gamma (IFN-gamma) or interleukin-1 (IL-1), is able to inhibit the induction of T-cell unresponsiveness in a dose-dependent fashion. Moreover, IL-2 was able to reverse established antigen-dependent T-cell unresponsiveness. In order to determine if modulation of IL-2 receptors is able to induce or abrogate unresponsiveness, the T cells were treated with anti-Tac antibody alone or together with tolerizing concentrations of antigen. Anti-Tac antibody was neither able to induce nor inhibit the induction of tolerance. The application of this model in the manipulation of immune responses is discussed here.
Essery
G
G
Charing Cross Sunley Research Centre, Hammersmith, London, U.K.
Feldmann
M
M
Lamb
J R
JR
D000941:Antigens / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D010455:Peptides / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D007375:Interleukin-1; D007376:Interleukin-2; D010455:Peptides; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma