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

Journal Article · · Journal of Immunology; (USA)
OSTI ID:6246124
; ; ; ;  [1]
  1. Univ. of Texas Southwestern Medical Center, Dallas (USA)
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 (greater than 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.
OSTI ID:
6246124
Journal Information:
Journal of Immunology; (USA), Journal Name: Journal of Immunology; (USA) Vol. 146:2; ISSN JOIMA; ISSN 0022-1767
Country of Publication:
United States
Language:
English