On the mechanisms of T cell silencing by IL-10 DNA: direct and indirect inhibition of T cell functions.
Previously we reported that mucosal IL-10 DNA administration resulted in long-term suppression of virus-induced inflammatory responses by silencing Th1-type CD4+ T cell functions. However, the mechanism by which IL-10 silences the activity of CD4+ T cells was not clear. The present report has shown that mucosal IL-10 DNA administration led to the reduction of reactivity of T cells following TCR stimulation. IL-10 DNA also downregulated APC functions to stimulate T cells but the effect was temporary. Bystander suppression, including that of IL-10 producing regulatory cells, appeared not to be directly involved in the inhibition of T cell reactivity because both anti-IL-10 and anti-IL-10R could not block the suppression of T cell functions. This silenced state could be maintained following adoptive transfer to untreated animals. The nature of the silencing appears to be a reversible anergic state since Ag stimulation in the presence of exogenous IL-2 restored T cell reactivity. Furthermore, IL-10-induced silenced T cells could be induced in vitro by culturing the T cells with rIL-10 in the presence or the absence of antigen stimulation. This state persisted in the absence of rIL-10 and persisted for at least 3 days. A more notable effect, however, was observed when the T cells were incubated with IL-10 in the presence of APC and Ag. These results indicate that IL-10 induced a long-term silenced state in T cells by direct and indirect inhibition of T cell functions.
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S K
SK
Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996, USA.
Chun
S
S
Lee
S
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Rouse
B T
BT
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005813:Genes, Synthetic; D005822:Genetic Vectors / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009092:Mucous Membrane / Q000737:chemistry; D010047:Ovalbumin / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013539:Simian virus 40 / Q000235:genetics; D018139:Simplexvirus / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D004274:DNA, Recombinant; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D016753:Interleukin-10; D010047:Ovalbumin