Document Detail

Tolerance induction by transcutaneous immunization through ultraviolet-irradiated skin is transferable through CD4+CD25+ T regulatory cells and is dependent on host-derived IL-10.
MedLine Citation:
PMID:  16456026     Owner:  NLM     Status:  MEDLINE    
UV radiation of the skin impairs immune responses to haptens and to tumor Ags. Transcutaneous immunization (TCI) is an effective method of inducing immune responses to protein and peptide Ag. We explore the effect of UV irradiation on TCI. The generation of Ag-specific CTL to OVA protein, but not class I MHC-restricted OVA peptide, is inhibited by TCI through UV-irradiated skin. Consequently, the induction of protein contact hypersensitivity and in vivo Ag-specific CTL activity following OVA protein immunization is prevented. Application of haptens to UV-exposed skin induces hapten-specific tolerance. We demonstrate that application of protein or class II MHC-restricted OVA peptide to UV-irradiated skin induces transferable Ag-specific tolerance. This tolerance is mediated by CD4(+)CD25(+) T regulatory (T(reg)) cells. These Ag-specific T(reg) cells inhibit the priming of CTL following protein immunization in the presence of CpG adjuvant. IL-10 deficiency is known to prevent hapten-specific tolerance induction. In this study, we demonstrate, using IL-10-deficient mice and adoptive T cell transfer, that IL-10 is required for the direct inhibition of CTL priming following immunization through UV-irradiated skin. However, IL-10 is not required for the induction of T(reg) cells through UV-irradiated skin as IL-10-deficient T(reg) cells are able to mediate tolerance. Rather, host-derived IL-10 is required for the function of UV-generated T(reg) cells. These experiments indicate that protein and peptide TCI through UV-irradiated skin may be used to induce robust Ag-specific tolerance to neo-Ags and that UV-induced T(reg) cells mediate their effects in part through the modulation of IL-10.
Mehran Ghoreishi; Jan P Dutz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  176     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-03     Completed Date:  2006-03-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2635-44     Citation Subset:  AIM; IM    
Department of Medicine and British Colombia Research Institute of Children and Women's Health, University of British Colombia, Vancouver, Canada.
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MeSH Terms
Antigens / immunology
CD4-Positive T-Lymphocytes / immunology*,  metabolism*
Immune Tolerance / immunology*
Interleukin-10 / deficiency,  genetics,  immunology*,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Peptides / immunology
Receptors, Interleukin-2 / immunology,  metabolism*
Skin / immunology*,  metabolism,  radiation effects*
Ultraviolet Rays
Reg. No./Substance:
0/Antigens; 0/Peptides; 0/Receptors, Interleukin-2; 130068-27-8/Interleukin-10

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