title: Regulatory T cells and IL-10 independently counterregulate cytotoxic T lymphocyte responses induced by transcutaneous immunization.
abstract: BACKGROUND
  The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI). Here we investigated the role of regulatory T cells (T(reg)) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses.
  
  
  RESULTS
  TCI was performed with an ointment containing the TLR7 agonist imiquimod and a CTL epitope was applied to the depilated back skin of C57BL/6 mice. Using specific antibodies and FoxP3-diphteria toxin receptor transgenic (DEREG) mice, we interrogated inhibiting factors after TCI: by depleting FoxP3(+) regulatory T cells we found that specific CTL-responses were greatly enhanced. Beyond this, in IL-10 deficient (IL-10(-/-)) mice or after blocking of IL-10 signalling with an IL-10 receptor specific antibody, the TCI induced CTL response is greatly enhanced indicating an important role for this cytokine in TCI. However, by transfer of T(reg) in IL-10(-/-) mice and the use of B cell deficient JHT(-/-) mice, we can exclude T(reg) and B cells as source of IL-10 in the setting of TCI.
  
  
  CONCLUSIONS
  We identify T(reg) and IL-10 as two important and independently acting suppressors of CTL-responses induced by transcutaneous immunization. Advanced vaccination strategies inhibiting T(reg) function and IL-10 release may lead the development of effective vaccination protocols aiming at the induction of T cell responses suitable for the prophylaxis or treatment of persistent infections or tumors.
authors: Institute for Immunology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors: Pamela
authors: P
authors: Stein
authors: Michael
authors: M
authors: Weber
authors: Steve
authors: S
authors: Prüfer
authors: Beate
authors: B
authors: Schmid
authors: Edgar
authors: E
authors: Schmitt
authors: Hans-Christian
authors: HC
authors: Probst
authors: Ari
authors: A
authors: Waisman
authors: Peter
authors: P
authors: Langguth
authors: Hansjörg
authors: H
authors: Schild
authors: Markus P
authors: MP
authors: Radsak
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D000077271:Imiquimod; D007108:Immune Tolerance; D007114:Immunization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10; D000077271:Imiquimod