Ultraviolet B radiation converts langerhans cells from immunogenic to tolerogenic antigen-presenting cells: Induction of specific clonal anergy in CD4+ T helper 1 cells

Jan C. Simon, Robert E. Tigelaar, Paul R. Bergstresser, Dale Edelbaum, Ponciano D Cruz

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220 Scopus citations

Abstract

We have recently demonstrated that a single dose (200 J/m2) of UVB radiation abrogates the capacity of mouse epidermal Langerhans cells (LC) or splenic adherent cells (SAC) to present keyhole limpet hemocyanin (KLH) to Ag-specific, MHC-restricted CD4+ Th1 cells. In the present study we determined whether such Th1 unresponsiveness represented long-lasting immunologic tolerance. To address this question, Th1 were preincubated with KLH-pulsed UVB-LC or UVB-SAC, then isolated and restimulated with unirradiated APC (LC or SAC) plus KLH or with exogenous rIL-2 in the absence of APC. Preincubation with KLH and UVB-LC or UVB-SAC rendered Th1 unresponsive to subsequent restimulation with APC and KLH. In addition, such Th1 were defective in their autocrine IL-2 production, but could respond normally to exogenous rIL-2, indicating that unresponsiveness was due to functional inactivation and not to cell death. Th1 unresponsiveness was Ag-specific, MHC-restricted, and long lasting (>16 days). In addition, it appears that Th1 unresponsiveness is not due to the release of soluble suppressor factors from UVB-LC or UVB- SAC because supernatants from such cells had no effect on Th1 proliferation. Addition of unirradiated allogeneic SAC during preincubation prevented the induction of unresponsiveness by UVB-LC or UVB- SAC, suggesting that UVB interferes with the capacity of LC or SAC to deliver a costimulatory signal(s) that can be provided by allogeneic SAC. We conclude that UVB can convert LC or SAC from immunogenic to tolerogenic APC.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalJournal of Immunology
Volume146
Issue number2
Publication statusPublished - Jan 15 1991

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ASJC Scopus subject areas

  • Immunology

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