Document Detail

Active induction of unresponsiveness (tolerance) to DNFB by in vivo ultraviolet-exposed epidermal cells is dependent upon infiltrating class II MHC+ CD11bbright monocytic/macrophagic cells.
MedLine Citation:
PMID:  7963554     Owner:  NLM     Status:  MEDLINE    
Contact sensitizers, tumor Ags, and microbial pathogens presented through UV-exposed skin result in T cell-mediated immune tolerance (inhibition of acquisition of responsiveness) to these normally potent immunogens. The APC in UV-exposed skin that delivers the signals inducing tolerance remains highly controversial and is the subject of this study. Application of the contact sensitizer, 2,4-dinitro-1-fluorobenzene (DNFB), to C3H/HeN mice immediately after a single dose of 72 mJ/cm2 UVB (138 mJ/cm2 total UVB) resulted in unresponsiveness to an initial DNFB ear challenge, but failed to block the development of responsiveness after a second sensitization on previously unexposed skin (no tolerance). A state of tolerance could only be achieved if a delay of 72 h was allowed to elapse between the UV exposure and the initial sensitization. Epidermal cell suspensions (EC) were prepared from the skin of normal controls and from skin exposed to the same UV dose 3 days before (UV-EC). Three days after in vivo UV exposure, Langerhans cells (CD11blow Ia+) were depleted, and CD11bbright Ia+ macrophages had appeared in the epidermis along with GR-1+ neutrophils. Intracutaneous injection of 2,4 dinitrobenzenesulfonic acid (DNBSO3)-haptenated UV-EC, but not normal controls, resulted in the induction of locally inducible Ag-specific tolerance to DNFB, indicating the presence and dominance of tolerogenic signal within in vivo-irradiated epidermis. Removal of CD11b+ and class II MHC+ cells within UV-EC showed that a CD11b+ class II MHC+ population was indeed critical for tolerance induction. In addition, tolerance induction by UV-EC was not a result of surviving, UV-exposed Langerhans cells, because haptenated 3-day cultured EC from epidermis removed 5 h after UV exposure (before leukocytic infiltration) failed to induce a tolerogenic state. In conclusion, the ability of UV-exposed skin to induce peripheral adult tolerance to a normally potent immunogen is critically dependent on inflammatory class II MHC+, CD11bbright monocytic/macrophagic cells that infiltrate UV-irradiated skin at the same time the ability to tolerize is acquired.
C Hammerberg; N Duraiswamy; K D Cooper
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  153     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1994-12-20     Completed Date:  1994-12-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4915-24     Citation Subset:  AIM; IM    
Department of Dermatology, University of Michigan, Ann Arbor 48109.
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MeSH Terms
Cells, Cultured
Dermatitis, Contact / immunology
Dinitrofluorobenzene / immunology*
Epidermis / immunology*,  radiation effects
Flow Cytometry
Haptens / immunology
Histocompatibility Antigens Class II / immunology*
Immune Tolerance / immunology*
Macrophage-1 Antigen / immunology*
Macrophages / immunology*
Mice, Inbred C3H
Ultraviolet Rays
Grant Support
R01 AR 41642-01A1/AR/NIAMS NIH HHS
Reg. No./Substance:
0/Haptens; 0/Histocompatibility Antigens Class II; 0/Macrophage-1 Antigen; 70-34-8/Dinitrofluorobenzene

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