Interleukin-21 inhibits dendritic cell-mediated T cell activation and induction of contact hypersensitivity in vivo.
Interleukin (IL)-21 is a newly described cytokine that is produced by activated T cells and displays structural homology to IL-4 and IL-15. We here analyzed the role of IL-21 in dendritic cell (DC)-induced, T cell-mediated contact hypersensitivity (CHS) in vivo and on T cell activation and unspecific mixed lymphocyte reaction in vitro. By PCR, we demonstrate here constitutive expression of the specific IL-21 receptor and the common gamma-chain in DC, which together are able to mediate IL-21 signaling. Short-time incubation of in vitro generated DC with IL-21 significantly reduced their potential to induce an antigen-specific CD8+ T cell proliferation. Interestingly, 2h incubation of these DC with IL-21 before injection completely inhibited the potential of these DC to induce a CHS reaction to the hapten fluorescein 5-isothiocyanate in vivo. Mice injected with IL-21-treated DC even failed to mount a CHS response after repetitive injection of non-IL-21-treated DC 2 weeks later, suggesting that an antigen-specific unresponsiveness can be induced by IL-21-treated DC. Our data demonstrate that IL-21 is a new modulator of DC-T cell interaction with the potential to induce DC-mediated antigen-specific tolerance.
Brandt
Katja
K
Research Center Borstel, Department of Immunology and Cell Biology, Borstel, Germany.
Bulfone-Paus
Silvia
S
Jenckel
André
A
Foster
Donald C
DC
Paus
Ralf
R
Rückert
René
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D000939:Epitopes; D007108:Immune Tolerance / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D000098546:Interleukin-21
D000939:Epitopes; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D000098546:Interleukin-21