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Regulatory T Cells and IL-10 Independently Counterregulate Cytotoxic T Lymphocyte Responses Induced by Transcutaneous Immunization

2011; Public Library of Science; Volume: 6; Issue: 11 Linguagem: Inglês

10.1371/journal.pone.0027911

1932-6203

Pamela Stein, Michael Weber, Steve Prüfer, Beate Schmid, Edgar Schmitt, Hans Christian Probst, Ari Waisman, Peter Langguth, Hansjörg Schild, Markus P. Radsak,

Immune Cell Function and Interaction

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 (Treg) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses. Methodology/Principal Findings 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 Treg in IL-10-/- mice and the use of B cell deficient JHT-/- mice, we can exclude Treg and B cells as source of IL-10 in the setting of TCI. Conclusion/Significance We identify Treg and IL-10 as two important and independently acting suppressors of CTL-responses induced by transcutaneous immunization. Advanced vaccination strategies inhibiting Treg 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.