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*2-CHLORO-1,3,5-TRINITROBENZENE
The Journal of Immunology, 2005, 174: 6677-6685.
Copyright © 2005 by The American Association of Immunologists, Inc.

Primary Defect in UVB-Induced Systemic Immunomodulation Does Not Relate to Immature or Functionally Impaired APCs in Regional Lymph Nodes1

Shelley Gorman*, Jamie W.-Y. Tan*, Jennifer A. Thomas*, Scott L. Townley{dagger}, Philip A. Stumbles*, John J. Finlay-Jones* and Prue H. Hart2,*

* Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia; and {dagger} School of Medicine, Flinders University, Adelaide, Australia

UVB irradiation of the shaved dorsal skin of mice can cause both local and systemic suppression of contact hypersensitivity responses; the former demonstrated by administration of the sensitizing Ag/hapten to the irradiated site and the latter by its administration at least 72 h later to distal unirradiated sites. The immunological basis of systemic immunomodulation is not clear. When haptens (trinitrochlorobenzene, FITC) were administered to the shaved ventral skin 4 days after irradiation (8 kJ/m2) to the shaved dorsum of BALB/c mice, CD11c+/FITC+ cells in the skin-draining lymph nodes from control and irradiated mice produced on a per cell basis similar levels of IL-12 and PGE2 were phenotypically mature and efficient at presenting FITC to lymphocytes from FITC-sensitized mice. Ag presentation by FACS-sorted CD11c+ lymph node cells isolated 4 days after UVB irradiation was as efficient as were cells from unirradiated mice at presentation in vitro of an OVA peptide (OVA323–339) to CD4+ cells from OVA-TCR-transgenic DO11.10 mice. Further, IFN-{gamma} levels were increased in the cultures containing CD11c+ cells from UVB-irradiated mice, suggesting that inflammation may precede downstream immunosuppression. These results suggest that the primary cause of reduced contact hypersensitivity responses in mice in which UV irradiation and the sensitizing Ag are applied to different sites several days apart must originate from cells other than CD11c+ APCs that directly or by production of soluble mediators (IL-12, PGE2) affect cellular responses in the nodes of UVB-irradiated mice.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Grant 229920 from the National Health and Medical Research Council of Australia.

2 Address correspondence and reprint requests to Dr. Prue Hart, Telethon Institute for Child Health Research, P.O. Box 855, West Perth, WA 6872, Australia. E-mail address: prueh{at}ichr.uwa.edu.au

3 Abbreviations used in this paper: DC, dendritic cell; CHS, contact hypersensitivity; MED, minimal erythemal dose; TNCB, trinitrochlorobenzene; GKN, 11 mM D-glucose, 5.5 mM KCl, 137 mM NaCl, 25 mM Na2HPO4, and 5.5 mM NaH2PO4·2H2O.




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