IL-20 receptor 2 signaling down-regulates antigen-specific T cell responses.
The recently described cytokines IL-19, IL-20, and IL-24 share structural homology with IL-10 and are therefore classified as members of the IL-10 family of cytokines. Although it has long been speculated that signaling by their heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2) influences immunological processes, the target cells for this group of cytokines are still unclear. By generating a knockout mouse strain deficient for the common IL-20R beta-chain (IL-20R2), we show that IFN-gamma and IL-2 secretion is significantly elevated after stimulation of IL-20R2-/--deficient CD8 and CD4 T cells with Con A or anti-CD3/CD28 in vitro. IL-10 secretion by activated IL-20R2-/- CD4 cells was diminished. Consistent with our in vitro results, significantly more Ag-specific CD8 IFN-gamma+ and CD4 IFN-gamma+ T cells developed to locally applied DNA vaccines in IL-20R2-deficient mice. In a T cell-dependent model of contact hypersensitivity, IL-20R2 knockout mice were more sensitive to the contact allergen trinitro-chloro-benzene. Thus, IL-20R2 signaling directly regulates CD8 and CD4 T cell answers in vitro and in vivo. For the first time, we provide evidence that IL-19, IL-20, and IL-24 are part of a signaling network that normally down-modulates T cell responses in mice.
Wahl
Christian
C
University Medical Center, Center of Internal Medicine, Department of Internal Medicine I, Ulm, Germany.
Müller
Werner
W
Leithäuser
Frank
F
Adler
Guido
G
Oswald
Franz
F
Reimann
Jörg
J
Schirmbeck
Reinhold
R
Seier
Anne
A
Weiss
Johannes Martin
JM
Prochnow
Blair
B
Wegenka
Ursula Maria
UM
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D000485:Allergens; D018984:Epitopes, T-Lymphocyte; D018123:Receptors, Interleukin; D019444:Vaccines, DNA; C492510:interleukin-20 receptor; D010853:Picryl Chloride